We could fill this entire website with research articles on dopamine and sexual function. Dopamine is the central player in sexual desire, erections, sexual fetishes and sexual addictions. When a porn user asks why they have sexual dysfunctions – the answer is dopamine. One of the most common complaints is erectile dysfunction, which is due to overstimulation of the reward circuitry.
Questions often arise about testosterone and heavy porn use. In some of these studies you will see that blood testosterone is not affected. Testosterone increases sexual desire by stimulating dopamine in the brain. Sexual satiety leads to fewer testosterone receptors, thus less dopamine.
Sexual function doesn’t correlate with blood levels of testosterone. Some heavy porn users report erectile dysfunction, which is likely due to “numbing their reward circuitry,” which involves a decline in key dopamine receptors. Giuliano F, Allard J. However, the exact involvement of dopamine in the control of sexual motivation and genital arousal in males is unknown. Experimental data in male rats suggested an implication of dopamine in sexual motivation as well as in copulatory performance.
A permissive role of dopamine released at the level of the median preoptic area of the hypothalamus in the display of copulatory behavior has also been demonstrated. It is noteworthy that these participations of the dopaminergic system are not specific for sexual behavior but rather reflect the involvement of dopamine in the regulation of cognitive, integrative and reward processes. Because of its role in the control of locomotor activity, the integrity of the nigrostriatal dopaminergic pathway is also essential for the display of copulatory behavior.
Somehow more specific to sexual function, it is likely that dopamine can trigger penile erection by acting on oxytocinergic neurons located in the paraventricular nucleus of the hypothalamus, and perhaps on the pro-erectile sacral parasympathetic nucleus within the spinal cord. In conclusion, central dopamine is a key neurotransmitter in the control of sexual function.
Full Study: Dopamine and sexual function Giuliano F, Allard J. Int J Impot Res.
Effect Of Sex On Women Penis Before After with How To Make A Penis Larger and Penis Before After
Groupe de Recherche en Urologie, UPRES, Medical University of Paris South, France.
However, the exact involvement of dopamine in sexual motivation and in the control of genital arousal in humans is unknown. In contrast, experimental data suggest an implication of dopamine at all these stages of the copulatory behaviour in rodents. The release of dopamine at the level of the nucleus accumbens, which is innervated by the mesolimbic dopaminergic pathway originating in the ventral tegmental area, is positively implicated in the pre-copulatory or appetitive phase in male rats.
There is also a permissive role in the copulatory or consumatory phase for dopamine released at the level of the median pre-optic area, which receives projection from the dopaminergic incertohypothalamic pathway within the hypothalamus. It is noteworthy that these participations of the dopaminergic system are not specific to sexual behaviour but rather reflect the more general involvement of dopamine in the regulation of cognitive, integrative and reward processes.
Due to its role in the control of locomotor activity, the integrity of the nigrostriatal dopaminergic pathway is also essential for the display of copulatory behaviour.
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The counterpart of such regulation of the genital arousal by dopamine has not yet been established in females. In conclusion, the central dopaminergic system is a key element of the control of sexual. COMMENTS: Excellent review of almost all the relevant research on androgen receptors, dopamine and sexual function.
Fantastic drawing the the hypothalamus-reward circuit interrelationships. In animal models of naturally rewarding behaviors, such as sex, testicular androgens contribute to the development and expression of the behavior in males. To effect behavioral maturation, the brain undergoes significant remodeling during adolescence, and many of the changes are likewise sensitive to androgens, presumably acting through androgen receptors AR.
Given the delicate interaction of gonadal hormones and brain development, it is no surprise that disruption of hormone levels during this sensitive period significantly alters adolescent and adult behaviors. In male hamsters, exposure to testosterone during adolescence is required for normal expression of adult sexual behavior. Males deprived of androgens during puberty display sustained deficits in mating.
Conversely, androgens alone are not sufficient to induce mating in prepubertal males, even though brain AR are present before puberty. In this context, wide-spread use of anabolic-androgenic steroids AAS during adolescence is a significant concern.
AAS abuse has the potential to alter both the timing and the levels of androgens in adolescent males. In hamsters, adolescent AAS exposure increases aggression, and causes lasting changes in neurotransmitter systems. In addition, AAS are themselves reinforcing, as demonstrated by self-administration of testosterone and other AAS. However, recent evidence suggests that the reinforcing effects of androgens may not require classical AR.
Therefore, further examination of interactions between androgens and rewarding behaviors in the adolescent brain is required for a better understanding of AAS abuse. Adolescence awakens the brain to both pleasure and risk. In human teenagers, this frequently takes the form of experimentation with drugs and sex. Likewise, this population has the highest rates of illicit drug use in the United States.
In addition, adolescence is a pivotal time in the etiology of certain psychopathologies, such as depression, anxiety, disordered eating, and conduct disorder. We posit that the pubertal secretion of gonadal hormones, their activation of steroid receptors in the brain, and the interaction between hormone and experience on adolescent brain development contribute to the behavioral changes seen during adolescence. Our goal here is to review the evidence that gonadal androgens mediate the adolescent maturation and adult performance of motivated behaviors, as well as the rewarding properties of these behaviors.
We also present evidence that testosterone itself is rewarding, which likely contributes to maturational changes in motivated behaviors during adolescence, when testosterone levels soar. The focus of this paper is on our studies of neural circuits underlying male sexual behavior, particularly in the Syrian hamster, with special emphasis on the interaction between testosterone and dopamine DA.
We propose that pubertal androgens have both transient and long-term effects on reward circuits and motivated behavior. We further hypothesize that supplementation with exogenous androgens in the form of anabolic-androgenic steroids AAS augments the normal influences of pubertal androgens, thereby adversely affecting adolescent development of brain and behavior.
Ultimately, the brain is both a trigger and a target for androgen action during adolescence. As secretion of luteinizing hormone from the anterior pituitary gland rises in response to hypothalamic gonadotropin-releasing hormone, circulating testosterone concentrations increase significantly.
Pubertal hormones act not only on peripheral tissues to cause the appearance of secondary sex characteristics that are the overt signs of puberty, but they also act centrally to influence both the remodeling of the adolescent brain and behavioral maturation. Thus, the pubertal increase in sex steroid hormones, driven by developmentally timed maturation of the reproductive neuroendocrine axis, in turn shapes adolescent behavioral development via both direct and indirect influences on the nervous system.
Human adolescence is now recognized as a major and dynamic period of neural development during which behavioral circuits are remodeled and refined. This concept was kindled by research in both humans and animals documenting that many of the basic developmental processes occurring during perinatal brain development are recapitulated during adolescence. Thus, the developmental trajectory of the postnatal brain is not linear, but is instead characterized by an adolescent burst of rapid change and involves both progressive and regressive events.
Thus, perturbations in the timing of pubertal hormone influences on the adolescent brain would be predicted to have long-lasting consequences for adult behavior. Because adolescence is a transient and dynamic phase of development, it would be difficult to evaluate the adolescent brain and behavior in isolation. Instead, to appreciate the unique character of adolescence, it is helpful to contrast it with the brain and behavior of mature adults.
Thus, with the focus of this paper on male sexual behavior and reward, it is important here to introduce the neural circuits for copulation and sexual motivation in adult males, including the role of gonadal steroid hormones in behavioral activation and the distribution of receptors for androgens AR and estrogens ER. AR are present in cell groups that form the neural circuits mediating rewarding social behaviors, such as sex. Not surprisingly, these effects follow a relatively slow time-course, with a delayed onset of action.
These steroid actions are thought to be mediated by non-genomic receptors. Initially, there is a modest increase in DA when a female is presented behind a screen. Not surprisingly, in castrated males that do not mate, MPOA DA does not increase Hull et al.
It is somewhat difficult to interpret this result, since the lack of DA release is confounded by the absence of sexual activity. However, DA release in MPOA correlates with the loss of mating in short-term castrates Hull et al. Within the rodent MPOA, the androgenic and estrogenic metabolites of testosterone play specific roles in the regulation of mating Putnam et al. The latency to initiate copulation mount or intromit is one measure of sexual motivation.
The latency to sexual activity is sensitive to estrogens, through maintenance of MPOA nitric oxide synthase, which in turn, maintains basal DA levels. Estrogen-treated castrates show high basal DA levels, which strongly correlate with the ability to initiate copulation. However, they fail to show female- and copulation-induced increases in DA release, which strongly correlate with sexual performance.
Consequently, their sexual performance is below intact levels. On the other hand, castrates treated with non-aromatizable androgen alone do not show elevated basal DA levels, and they fail to initiate copulation.
For normal sexual performance, therefore, both estrogens and androgens are required. Sexual performance is usually expressed as frequency measures of mounts, intromissions, and ejaculations. Only when both estrogens and androgens are replaced, do castrated males exhibit elevated DA levels and shorter latency measures and female- and copulation-induced DA increases and increased frequency measures.
In this manner, estrogens in MPOA contribute to sexual motivation, and both estrogens and androgens to sexual performance. Although testosterone is necessary for MPOA DA release during male copulatory behavior and for mating itself, neither testosterone nor mating alone can elicit DA in MPOA. Instead, chemosensory cues from conspecific females are also required for DA release in MPOA.
In rodents, chemosensory stimuli are the primary sensory modality to initiate male sexual behavior Fig. Although bilateral removal of the olfactory bulbs eliminates sexual activity and MPOA DA release, unilateral bulbectomy does not interfere with mating. In this study, copulation induced MPOA DA release when measured contralateral to the lesioned olfactory bulb, but not in the ipsilateral hemisphere Fig. Taken together, these data suggest that testosterone creates a permissive environment that allows external sensory stimuli to reach MPOA and induce DA release during copulation.
Ultimately, sexual behavior and other natural rewards activate neural reward pathways. The mesocorticolimbic DA circuit consists of the ventral tegmental area VTAnucleus accumbens Acband prefrontal cortex Pfc. In this manner, testosterone has the potential to affect the release of DA in Acb both through its enhancement of sexual behavior, and through its actions as a drug of abuse see below. Current evidence suggests that the mesocorticolimbic DA system matures during adolescence.
Our data show that androgen-sensitive cells in male hamsters project to the VTA from structures associated with steroid-sensitive behaviors.
These projections provide an opportunity for androgens to modify the activity of the mesocorticolimbic DA system. The traditional view of hormone action on adolescent behavior is based on activational effects of steroid hormones, which refer to the ability of steroids to facilitate behavior in specific social contexts by action within target cells in the neural circuits underlying behavior. Activational effects are transient in the sense that they come and go with the presence and absence of hormone, and they are typically associated with the expression of adult behavior.
In contrast, organizational effects refer to the ability of steroids to sculpt nervous system structure during development. Structural organization is permanent, persists beyond the period of exposure to hormone, and determines neural and behavioral responses to steroids in adulthood. And, like other periods of rapid developmental change, adolescence represents a defined window of opportunity for steroid-dependent brain remodeling.
Before puberty, testosterone treatment cannot activate sexual behavior in hamsters, suggesting that maturational processes that render neural circuits susceptible to activation or organization by steroid hormones have not yet occurred Meek et al.
Conversely, while the overt expression of male reproductive behavior in adulthood does not absolutely require the presence of gonadal steroids during adolescence, the maximal expression of behavior does.
Moreover, deficits in reproductive behavior are long-lasting, and cannot be overcome either by prolonged testosterone treatment or by sexual experience in adulthood Schulz et al. Similarly, after treatment with estrogen and progesterone, NoT P males display shorter lordosis latencies and longer lordosis durations than males castrated as adults Schulz et al. It may be that NoT P males suffer from decreased sexual motivation. One way to address this question is to compare the latencies to engage in both ano-genital investigation AGI and mounting between males gonadectomized before NoT P and after puberty T P.
If sexual motivation is dependent on gonadal hormone exposure during adolescence, we would predict longer latencies to engage in sexual behavior in NoT P males.
Indeed, with repeated exposure to estrous females, NoT P males take longer to begin AGI and mounting compared with T P males Fig. Thus, in addition to organizing aspects of sexual performance, it appears that pubertal hormones also organize the rewarding aspects of sexual behavior.
Nonetheless, many interesting questions remain. Would a NoT P male barpress for an estrous female or develop a conditioned place preference for a mating location? Future research will explore the role of pubertal hormones in organizing sexual motivation and sexual performance.
Anogenital investigation AGI latencies and durations exhibited by male hamsters gonadectomized before puberty NoT P or after puberty T P.
T P males showed similar AGI latencies across the three tests with an estrous female, whereas NoT P males increased AGI latencies during the third test with an estrous female.
T P males decreased mount latencies across the three behavior tests with an estrous female, whereas noT P males showed no change in mount latency across the three behavior tests. These data suggest that pubertal gonadal hormones have lasting, facilitatory effects on adult male motivation to engage in sexual behavior with a female. Unpublished data from animal subjects in Schulz, K.
One of the enduring puzzles of adolescent behavioral development is why activation of reproductive behavior in response to steroid exposure is attenuated in prepubertal male hamsters.
If low levels of androgens before puberty limit the expression of male sexual behavior in prepubertal males, then supplementing endogenous androgens in prepubertal males should elicit mating. This turns out not to be the case Meek et al. Therefore, it appears that androgens and AR are necessary but not sufficient for expression of male sexual behavior. Efforts to identify factors that limit sexual activity before puberty have thus far been mixed.
These data demonstrate that sensory transduction mechanisms are mature before puberty. One potential explanation is that prepubertal males are not motivated to engage in sexual behavior. Thus, female pheromones appear to be an unconditioned stimulus for neurochemical and neuroendocrine responses in adult, but not prepubertal males, suggesting that the salience of these socially relevant sensory stimuli changes over pubertal development, possibly related to the acquisition of rewarding properties and sexual motivation.
In addition, although testosterone does facilitate AGI of a female in prepubertal males, this effect depends on whether or not the male has had previous exposure to an estrous female. Furthermore, prepubertal males that have had one previous experience with a female display much longer AGI latencies and shorter AGI durations than males interacting with receptive females for the first time Fig. These data suggest that interactions with an estrous female are aversive rather than rewarding prior to puberty, thereby eliminating any facilitating effects of testosterone on AGI during subsequent interactions with a female.
Prepubertal and adult male medial preoptic area MPOA dopaminergic responses to female pheromones contained in vaginal secretions. Adult males show increases in MPOA dopaminergic activity with exposure to female vaginal secretions, whereas prepubertal males do not display increased MPOA dopaminergic responses to female pheromones. Redrawn from Schulz, K. Males exposed to testosterone prepubertally also displayed more intromissions in adulthood than males exposed to testosterone during or after puberty Schulz et al.
These data suggest that the ability of testosterone to organize behavioral neural circuits decreases with age, and that adolescence marks the end of a protracted postnatal sensitive period for exposure to testosterone. The preceding data suggest that endogenous gonadal steroids enhance motivated behaviors during adolescence. AAS are used principally for their anabolic muscle-building effects. However, as their name implies, AAS also have androgenic properties. Testosterone is a logical choice in animal studies for exploring fundamental mechanisms of androgen reward.
It remains a popular choice for human users as well, most often in the form of long-acting testosterone esters such as testosterone propionate. At high doses, AAS produce significant behavioral changes. In particular, because of their close relationship to testosterone, AAS use in the teen years would appear to perturb the normal steroid milieu of the developing human adolescent nervous system, including the quantity, timing, and type of steroid exposure.
As with other illicit drugs, human AAS abuse is a problem of adolescence. Inappropriate aggression is the behavioral response most often associated with human AAS abuse.
However, given the range of androgen exposures, the variety of psychiatric symptoms, and the potential for pre-existing psychiatric dysfunction, it is difficult to determine the precise role of AAS in these cases of human aggression. Nonetheless, it is important to keep in mind that the doses administered to human volunteers are much lower than the doses advocated on body building websites, and the duration of treatment is generally short.
Thus, on balance, it seems to fair to conclude that AAS have the potential to enhance agonistic behavior, at least in susceptible individuals. Animal studies have also provided compelling evidence for AAS-induced aggression. These behavioral changes are accompanied by lasting remodeling of neural circuitry in the anterior hypothalamus. It should come as no surprise that AAS alter brain levels of AR as well.
Thus, there is the potential for AAS to enhance androgen-dependent behaviors both by supplementing endogenous androgens and by increasing androgenic responsiveness via increased AR expression. However, neither testosterone nor nandrolone enhanced mating in adolescent male rats.
It is particularly important to note that adolescent and adult hamsters can show different behavioral responses to AAS exposure. This is consistent with the concept of adolescence as a sensitive period for androgen action. Thus, the effects of AAS change across adolescent development, and adolescent AAS exposure can cause excessive aggressive and sexual behavior patterns that may persist into adulthood. Mating and fighting are each rewarding at least if you win the fight.
If AAS can enhance rewarding social behaviors above levels normally observed in gonad-intact males, it is logical to expect that testosterone itself might be rewarding.
This has been tested using two well-established animal models for reward and reinforcement: CPP and self-administration. The results of these studies demonstrate that testosterone is reinforcing in an experimental context where anabolic effects and athletic performance are irrelevant. With CPP, the test substance is repeatedly paired with a unique environment for example, a particular chamber in the testing apparatus.
Once the animal associates the reinforcing test substance with that environment, he will seek out the environment even in the absence of reward. Intravenous delivery eliminates potential confounding effects of taste or gut fill on androgen intake.
In the context of AAS abuse, it is important to differentiate between central and peripheral effects of androgens. In other words, maybe testosterone reduces muscle fatigue and improves joint function so that animals just feel better. Likewise, our laboratory has demonstrated intracerebroventricular icv testosterone self-administration in male hamsters Wood et al. Intracerebral CPP and icv self-administration with testosterone argue for central targets mediating androgen reinforcement.
It is notable that testosterone reinforcement does not necessarily follow the same mechanisms previously established for steroid effects on sexual behavior. This suggests that other brain regions are important for androgen reinforcement.
In contrast, male rats will form a CPP to testosterone injections in Acb Packard et al. However, unlike other drugs of abuse, our studies in hamsters suggest that testosterone does not induce Acb DA release Triemstra, Sato, and Wood, in press. Together, these data suggest that although testosterone reinforcement may ultimately alter DA activity in Acb, the mechanisms may be distinct from those of cocaine or other stimulants.
At the present time, the specific steroid signals, receptors and brain sites of action for testosterone reinforcement are unknown. This implies that both AR and ER may transduce steroidal stimuli for reward. There is the additional possibility that testosterone reinforcement may be mediated by a combination of classical and non-genomic receptors. Several lines of evidence point to the actions of non-genomic receptors in the reinforcing effects of AAS.
Accordingly, to test the role of non-genomic AR in AAS reinforcement, we utilized two complementary techniques Fig. The Tfm mutation greatly diminishes ligand binding at AR. Nonetheless, Tfm rats and their wild-type male siblings self-administered roughly the same amount of DHT.
This argues for non-genomic effects of DHT. In a subsequent study, we determined if male hamsters would self-administer DHT conjugated to bovine serum albumin BSA, Fig. They showed a similar preference for DHT-BSA conjugates, but failed to self-administer BSA alone. These data point toward a central role for cell surface ARs in androgen reinforcement. Currently, the exact nature of such receptors is not known. This may be in the form of extra-nuclear classical AR as reported in hippocampus Sarkey et al.
Alternatively, previous studies have also described steroid-binding sites on other neurotransmitter systems. This is an important area for future research.
Why should there be a membrane AR? As discussed previously, there is a close association between androgen secretion and rewarding social behaviors. We can speculate that the increase in testosterone secretion that follows mating or fighting serves to reinforce the behavior. If so, it is necessary to have a rapid coupling of stimulus behavior and reward testosterone.
This can best be achieved through binding to membrane AR. In this regard, it would be of interest to determine if clamping androgen secretion during mating reduces the rewarding effects of sexual behavior. Here we review the evidence that androgens are potent mediators of adult motivated behaviors, and further, that the timing of androgen exposure during development programs androgen-dependent motivated behavior in adulthood.
Anabolic steroids are fast becoming a favored drug of abuse by adolescents in the US. While AAS may not have the addictive potency of cocaine or heroin, we are just beginning to understand the potential for androgen reinforcement and addiction. In particular, as youth sports become more competitive, there is increasing pressure on developing athletes to use steroids, starting at younger ages.
This trend is troubling in view of new evidence for steroid-sensitive neural maturation in adolescents. Despite increased awareness by both the public and scientific communities of the profound neural changes accompanying adolescence, experimental study of the developmental neurobiology of puberty has been limited.
Animal models of pubertal timing will also inform human research efforts, and potentially lead to more effective therapeutic interventions during adolescence. We thank Eleni Antzoulatos, Cortney Ballard, Lucy Chu, Kelly Peters, Jennifer Triemstra, Jane Venier, Lisa Rogers, and Pamela Montalto for assistance with these studies.
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They are taken in large quantities by athletes and others to increase performance, with negative health consequences. However, the relative abuse and dependence liability of AAS have not been fully characterized. In humans, it is difficult to separate the direct psychoactive effects of AAS from reinforcement due to their systemic anabolic effects.
However, using conditioned place preference and self-administration, studies in animals have demonstrated that AAS are reinforcing in a context where athletic performance is irrelevant.
Furthermore, AAS share brain sites of action and neurotransmitter systems in common with other drugs of abuse. In particular, recent evidence links AAS with opioids. In humans, AAS abuse is associated with prescription opioid use. In animals, AAS overdose produces symptoms resembling opioid overdose, and AAS modify the activity of the endogenous opioid system. Montorsi FPerani DAnchisi DSalonia AScifo PRigiroli PZanoni MHeaton JPRigatti PFazio F.
Department of Urology, University Vita Salute San Raffaele, Milano, Italy. Yet, only recently, was a centrally acting agent, apomorphine sublingual, approved for the treatment of erectile dysfunction. The present functional magnetic resonance imaging placebo-controlled study presents the first in vivo demonstration of the apomorphine-induced modulation of cortical and subcortical brain structures in patients with psychogenic erectile dysfunction.
Noteworthy, patients in comparison with potent controls, showed an increased activity in frontal limbic areas that was downregulated by apomorphine. This suggests that psychogenic impotence may be associated with previously unrecognized underlying functional abnormalities of the brain. Nickel MMoleda DLoew TRother WPedrosa Gil F.
Cabergoline treatment was well-tolerated and resulted in normalization of hormone levels in most cases. In the cabergoline-treated group, significant interactions between prolactin and testosterone serum concentrations were observed. Erectile function improved significantly. Sexual desire, orgasmic function, and the patient’s and his partner’s sexual satisfaction were also enhanced. Cabergoline may be an effective and safe alternative agent for men with psychogenic ED. Ovariectomized females were induced into estrus with hormonal injections, and males interacted with a different female each day.
Additionally, blood was collected every other day following sexual interactions to assess serum testosterone levels. Testosterone was found to peak on the first day of interaction and then fell back to near the level of control rats that did not interact with females. Following the initial peak, testosterone concentrations fluctuated less in males exposed to females than in controls. Sexual activity was not found to predict testosterone concentration. We conclude that when male rats have daily sexual interactions, sexual behavior tends to show cyclic changes and testosterone is significantly elevated only on the first day of interactions.
Bell and Cheryl L. Naturally occurring developmental changes in male Syrian hamster responses to a salient social cue, female hamster vaginal secretions VSprovide a good model system for investigating neuroendocrine mechanisms of adolescent change in social reward.
In this series of experiments, the authors examined the roles of testosterone and dopamine receptor activation in mediating the adolescent gain in positive valence of VS. Together, these studies demonstrate that the unconditioned rewarding properties of a social cue necessary for successful adult sociosexual interactions come about as the result of the pubertal increase in circulating testosterone in male hamsters.
Given the necessity of appropriately interpreting social stimuli in successful adult social interactions and reproductive fitness, a fundamental problem for developmental psychobiology is the identification of the neuroendocrine mechanisms underlying adolescent maturation of social information processing. However, it is unknown whether the reinforcing value of VS is similarly testosterone-dependent in either adult or juvenile hamsters.
Specifically, dopamine has been implicated in multiple aspects of sexual reward. It remains to be determined whether dopamine receptor activation is necessary for CPP to VS in male hamsters. However, we do know that behavioral differences between gonad-intact juvenile and adult hamsters are mirrored by their dopaminergic responses to VS.
Thus, gain of dopaminergic function across adolescence may be necessary for VS reward and attraction. Dopaminergic involvement in sexual reward is regulated by testosterone in rodents. Therefore, this series of studies tested the hypothesis that testosterone activates social reward via influences on dopaminergic reward circuitry, using the formation of CPP to VS in adult and juvenile male hamsters as a model system.
Female hamsters were ovariectomized several weeks before hormone administration for experimental control of day of hormone-induced estrus, when VS secretion is maximal. Hamsters were treated in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animalsand protocols were approved by the Michigan State University Institutional Animal Care and Use Committee. Hamsters in gonadectomized GDX experimental groups underwent surgery with isoflurane anesthesia.
Bilateral longitudinal scrotal incisions were made, and the testes were removed with a cut distal to ligature adults or cauterization juveniles. These outer compartments were designed to allow for compartment-specific associations, with distinct visual, tactile, and olfactory cues. The outer compartment in which the hamster spent more time was defined as the initially preferred compartment. Animals were assigned to experimental and control groups so as to equate groups for initial chamber preferences and preference scores and litter representation in the different groups.
During the no-stimulus conditioning sessions, hamsters in both the experimental and the control groups were placed in their initially preferred compartments, where they remained alone.
During stimulus-paired conditioning sessions, hamsters in the experimental group were placed in the initially nonpreferred compartments with the stimulus. The hamsters in the control groups were also placed in their initially nonpreferred compartments but were not given the stimulus.
This group served to quantify any changes in preference or difference score across tests that were attributable to habituation during conditioning. Immediately before testing, the tube was placed out of reach from the male at the top of the back wall in the initially nonpreferred compartment in VS-paired conditioning sessions for the VS group. Empty Eppendorf tubes were used for the control group in all conditioning sessions and for the VS group in the no-stimulus conditioning sessions.
Clean oil was applied to the nose of hamsters in the control group for all conditioning sessions and those in the VS group for no-stimulus conditioning sessions. Twenty-four hours after the last conditioning session, hamsters were tested for their place preference following the same procedure used for the pretest. As in the pretest, no stimulus was present, and preference and difference scores were calculated for each animal.
This experiment tested whether circulating testicular hormones are required for the display of a CPP to VS in adult hamsters. This experiment tested the involvement of dopamine in testosterone-facilitated CPP to VS in juvenile male hamsters.
A similar conditioning paradigm was used as that described, but haloperidol was given in the initially preferred chamber in an attempt to reduce initial preferences, and no VS were used. Locomotor movement number of changes in infrared beam breaks and fecal boli output during conditioning sessions were also quantified as indicators of physiological effects of haloperidol. This experiment determined whether haloperidol reduces attractive properties of VS.
The location of the smell was counterbalanced across groups and within an animal. Animals remained in their colony room until immediately before testing. To confirm that all control and experimental groups had similar initial preference and difference scores, a one-way ANOVA was used. Changes in preference and difference scores were determined by subtracting pretest measures from test measures for each hamster.
In the control animals, average change measures for preference score and difference score were determined to provide a standard for unconditioned change.
Control change measures in preference and difference scores was then subtracted from each experimental animal’s scores to correct for any unconditioned change. Therefore, control measures are not shown in figures.
Significant changes in both preference and difference scores were required to conclude that a CPP had been established. Measures from vehicle injections on the first and last day of testing did not differ and were averaged together per animal. A repeated measures ANOVA was used to determine the effects of drug on the number of line crossings, to indicate effects of drug on locomotor activity. Therefore, recent exposure to testicular hormones is necessary for VS-induced CPP.
A CPA to the highest dose of haloperidol was detected. Thus, haloperidol significantly reduced attraction to VS at some doses. Groups of the same age did not differ in body weight. These studies demonstrate that the perception of a species-specific chemosensory stimulus as rewarding is testosterone dependent and involves activation of dopamine receptors.
Specifically, we found that long-term GDX adult male hamsters do not form a CPP to VS, whereas testosterone treatment of juveniles is sufficient to enable them to form a CPP to VS. We infer from these findings that adolescent maturation of social information processing is the result of the pubertal increase in circulating testosterone that, via yet unidentified influences on dopaminergic circuits, results in the perception of female chemosensory stimuli and environments associated with those stimuli as rewarding.
This blockade is due to a reduction in the attractive and rewarding properties of VS, as demonstrated by the unconditioned attraction test. Additionally, haloperidol did not affect movement and affected fecal boli output only at the highest dose. Although the site s of action of dopamine cannot be determined from this study, there are several likely candidates. Thus, dopamine action in the MPOA, Acb, or both regions may be important for CPP to VS.
However, the hormone sensitivity of the adult MPOA is well-established. Thus, it is plausible that the normative increase in circulating testosterone during adolescence promotes dopaminergic release in response to VS, in MPOA, Acb, or both, thereby promoting VS reward. Taken together, these studies demonstrate the importance of testosterone and dopamine in rewarding responses to an unconditioned social stimulus. Both testosterone and dopamine systems mature during adolescence, when the rewarding quality of VS typically is acquired.
It should be noted that the dopaminergic circuit could be functional in juvenile animals to mediate CPP to VS, but that testosterone-dependent activation of some other neural circuitry is also necessary for VS reward.
However, the most parsimonious explanation, given the supporting evidence, is that testosterone treatment in juvenile animals mimics the normative elevation in pubertal testosterone, which in turn affects the dopaminergic system to permit VS reward. The authors gratefully acknowledge Jane Venier, Andrew Kneynsberg, Elaine Sinclair, Susie Sonnenschein, Joshua Paasewe, Jennifer Lampen, and Shannon O’Connell for their many hours helping with CPP.
In addition, the authors appreciate the helpful feedback on experimental design and writing from Kayla De Lorme and Maggie Mohr. The medial preoptic area MPOAsupraoptic nucleus SON and paraventricular nucleus PVN of the hypothalamus may serve as candidate sites because they contain oxytocin cells, receive dopaminergic inputs and have been implicated in mediating masculine sexual behavior.
Together, the data suggest dopamine’s effects on hypothalamic oxytocin cells during penile erection are context-specific. Dopamine may act via different parvocellular and magnocellular oxytocin subpopulations to elicit erectile responses, depending upon whether intromission is performed.
This study demonstrates the potential existence of interaction between central dopamine and oxytocin pathways during penile erection, with the SON and PVN serving as integrative sites. Notably, more penile erections and yawns were recorded mainly in the ascending part of these curves e. The present study confirms and extends previously reported differences in dopamine transmission between RLA and RHA rats and between the SD strain and the Roman lines.
Brodie Department of Neuroscience and Centre of Excellence for the Neurobiology of Addictions, University of Cagliari, Italy. This increases the production of nitric oxide, which activates oxytocinergic neurotransmission in extra-hypothalamic brain areas and spinal cord, leading to penile erection and yawning. Oei NYRombouts SASoeter RPvan Gerven JMBoth S. Leiden Institute for Brain and Cognition-LIBC, Leiden University, Leiden, The Netherlands.
Previous studies have shown that subconscious subliminal presentation of sexual stimuli activates brain areas known to be part of the ‘reward system’. In this study, it was hypothesized that dopamine modulates activation in key areas of the reward system, such as the nucleus accumbens, during subconscious processing of sexual stimuli.
Brain activation was assessed during a backward-masking task with subliminally presented sexual stimuli. Results showed that levodopa significantly enhanced the activation in the nucleus accumbens and dorsal anterior cingulate when subliminal sexual stimuli were shown, whereas haloperidol decreased activations in those areas. Dopamine thus enhances activations in regions thought to regulate ‘wanting’ in response to potentially rewarding sexual stimuli that are not consciously perceived.
This running start of the reward system might explain the pull of rewards in individuals with compulsive reward-seeking behaviors such as hypersexuality and patients who receive dopaminergic medication.
Comments: Continued evidence that dopamine regulates male sexual behavior and the hypoathlamus is a central player. I suspect that porn-induced ED involves changes in the sexual centers of the hypothalamus. The medial preoptic area MPOAat the rostral end of the hypothalamus, is important for the regulation of male sexual behavior. Results showing that male sexual behavior is impaired following MPOA lesions and enhanced with MPOA stimulation support this conclusion.
The neurotransmitter dopamine DA facilitates male sexual behavior in all studied species, including rodents and humans. Here, we review data indicating that the MPOA is one site where DA may act to regulate male sexual behavior.
DA agonists microinjected into the MPOA facilitate sexual behavior, whereas DA antagonists impair copulation, genital reflexes, and sexual motivation.
Moreover, microdialysis experiments showed increased release of DA in the MPOA as a result of precopulatory exposure to an estrous female and during copulation. DA may remove tonic inhibition in the MPOA, thereby enhancing sensorimotor integration, and also coordinate autonomic influences on genital reflexes. In addition to sensory stimulation, other factors influence the release of DA in the MPOA, including testosterone, nitric oxide, and glutamate.
Here we summarize and interpret these data Behav Neurosci. Those data suggest that the steroid-dependent role of hypothalamic DA in male sexual behavior has been conserved through evolutionary time. Dopamine release in the medial preoptic area is related to hormonal action and sexual motivation. If there is dopamine dysfunction, as is often the case with heavy porn use, then all the testosterone in the world will not help with erections and libidos.
Putnam SK, Sato S, Hull EM. The medial preoptic area MPOA is an important integrative site for male sexual behavior. Dopamine DA is released in the MPOA of male rats shortly before and during copulation. The recent presence of testosterone T may be necessary for this precopulatory increase in release. Previously, the postcastration loss of copulatory ability mirrored the loss of the DA response to an estrous female, and the restoration of copulation with exogenous T was concurrent with the reemergence of this DA response.
The present study investigated the effectiveness of the two major metabolites of T in maintaining copulation and basal and female-stimulated DA levels. Microdialysis samples were collected from the MPOA during baseline conditions, exposure to an estrous female behind a barrier, and copulation testing. These results suggest that ESTROGEN maintains normal basal levels of extracellular DA in the MPOA, which are sufficient for suboptimal copulation, but that ANDROGEN is required for the female-stimulated increase in DA release and for facilitation of ejaculation.
Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, The Netherlands. Abstract Correlational evidence in humans shows that levels of the androgen hormone testosterone are positively related to reinforcement sensitivity and competitive drive.
Structurally similar anabolic-androgenic steroids AAS are moreover widely abused, and animal studies show that rodents self-administer testosterone. These observations suggest that testosterone exerts activational effects on mesolimbic dopaminergic pathways involved in incentive processing and reinforcement regulation.
However, there are no data on humans supporting this hypothesis. We used functional magnetic resonance imaging fMRI to investigate the effects of testosterone administration on neural activity in terminal regions of the mesolimbic pathway. During MRI scanning, participants performed a monetary incentive delay task, which is known to elicit robust activation of the ventral striatum during reward anticipation.
Results show a positive main effect of testosterone on the differential response in the ventral striatum to cues signaling potential reward versus nonreward. Notably, this effect interacted with levels self-reported intrinsic appetitive motivation: individuals with low intrinsic appetitive motivation exhibited larger testosterone-induced increases but had smaller differential responses after placebo. Thus, the present study lends support to the hypothesis that testosterone affects activity in terminal regions of the mesolimbic dopamine system but suggests that such effects may be specific to individuals with low intrinsic appetitive motivation.
By showing a potential mechanism underlying central reinforcement of androgen use, the present findings may moreover have implications for our understanding of the pathophysiology of AAS dependency. COMMENTS: Many cite this study as evidence that abstinence increases testosterone. It seems to be saying exactly that in the bolded sentence, but its not. Read the FULL study and view the graph for testosterone. Hormonal and cardiovascular parameters were examined in ten healthy adult men during sexual arousal and masturbation-induced orgasm.
Blood was drawn continuously and cardiovascular parameters were constantly monitored. Plasma was subsequently analysed for concentrations of adrenaline, noradrenaline, cortisol, prolactin, luteinizing hormone and testosterone concentrations.
Orgasm increased blood pressure, heart rate, plasma catecholamines and prolactin. These effects were observed both before and after sexual abstinence.
In contrast, although plasma testosterone was unaltered by orgasm, higher testosterone concentrations were observed following the period of abstinence. These data demonstrate that acute abstinence does not change the neuroendocrine response to orgasm but does produce elevated levels of testosterone in males. Buvat JLemaire A. Association pour l’Etude de la Pathologie de l’Appareil Reproducteur et de la Psychosomatique, Lille, France. Testosterone and prolactin were determined by radioimmunoassay.
Determination was repeated in case of abnormal first results. Main clinical criteria tested regarding efficiency in hormone determination were low sexual desire, small testes and gynecomastia.
Endocrine therapy consisted of testosterone heptylate or human chorionic gonadotropin for hypogonadism and bromocriptine for hyperprolactinemia. Two pituitary tumors were discovered after testosterone determination. Low prevalences and effects of low testosterone and high prolactin in erectile dysfunction cannot justify their routine determination.
COMMENTS – Study finds that Viagra can increase dopamine in the reward center and in the hypothalamus. Kyratsas CDalla CAnderzhanova EPolissidis AKokras NKonstantinides KPapadopoulou-Daifoti Z. Sildenafil is the first effective oral treatment for male erectile dysfunction.
Although it is generally accepted that its action is peripheral, it has been suggested that it influences central neural pathways that are involved in male sexual arousal. Recently, it was shown that local sildenafil administration enhances extracellular dopamine DA in the nucleus accumbens NAcc.
The aim of this study was to determine whether sildenafil administration alters dopaminergic and serotonergic activity in the NAcc and the medial preoptic area mPOA during a model of sexual arousal. Thirty minutes after the last sildenafil injection, all males were exposed to noncontact erection sessions by the presentation of inaccessible estrous females. Half of the males had previous experience of noncontact sexual encounter and the other half were exposed for the first time.
Our data confirm that sildenafil enhances dopaminergic activity in the NAcc, extend these findings to the mPOA and furthermore, reveal sildenafil-induced effects on serotonergic activity in these brain regions as well. Therefore, present findings support an effect of sildenafil on central neural pathways that are involved in the control of sexual arousal. COMMENTS: Testosterone injected into the reward circuit is rewarding in ways similar to addictive drugs – that is testosterone induces conditioned place preference.
Packard MGSchroeder JPAlexander GM. Previous evidence indicates that peripheral and intranucleus accumbens injections of testosterone have rewarding effects in male rats as measured in a conditioned place preference CPP paradigm. The present study investigated the neurochemical bases of the rewarding properties of testosterone by examining the effect of peripheral and intranucleus accumbens injection of the dopamine receptor antagonist alpha-flupenthixol on expression of testosterone -induced CPP.
On the test day, rats receiving saline injections spent significantly more time in the compartment previously paired with injections of testosterone than in the compartment previously paired with vehicle injections. In contrast, rats receiving peripheral or intra-accumbens alpha-flupenthixol injections did not spend significantly more time in the compartment previously paired with testosterone.
The blockade of testosterone CPP was not due to an effect of alpha-flupenthixol on motor behavior. The findings provide further evidence of the rewarding affective properties of testosterone and indicate that peripheral administration and intra-accumbens administration of alpha-flupenthixol block expression of testosterone CPP.
The rewarding affective properties of testosterone are mediated, at least in part, via an interaction with the mesolimbic dopamine system. One way to evaluate sexual arousal is by measuring approach behavior to sexual incentive stimuli. In our case we measure approach behavior to an originally non-preferred compartment which is associated with the physiological state induced by mating. This change of preference indicative of a positive affective reward state can be evaluated by conditioned place preference CPP.
We have shown that the CPP induced by paced mating is mediated by opioids. The administration of opioids also induces a reward state. The present study was designed to compare the rewarding properties of paced mating and a morphine injection.
One group of females was allowed to pace the sexual interaction before being placed in the non-preferred compartment. In alternate sessions they received a morphine injection before being placed in the preferred compartment. In another group of females, the treatments were reversed.
These results further demonstrate the biological relevance associated with the ability of the female to space coital stimulation received during mating. This positive affective state will contribute to increase sexual arousal the next time a rat finds an appropriate mate.
Dopamine DA activity in the medial preoptic area MPOA contributes to the control of male rat sexual behavior. Extracellular DA and its metabolites in male rats’ MPOA were measured using microdialysis. When the barrier was removed and the animals were allowed to copulate, levels of DA and its metabolites continued to rise in intact males and in castrates that copulated. The DA response to the estrous female could not be attributed to nonsexual social stimuli, since exposure to another male was ineffective.
The DA response to copulation could not be attributed primarily to motor activity, since animals running voluntarily in a running wheel did not show significantly increased DA. These and previous data suggest that DA released in the MPOA in response to an estrous female may contribute to sexual motivation and copulatory proficiency. Testosterone may promote copulation in part through permissive actions on dopamine release. Puts ab,Lauramarie E.
Pope aAlexander K. Hill aRodrigo A. Wheatley aS. Marc Breedlove Across human societies and many nonhuman animals, males have greater interest in uncommitted sex more unrestricted sociosexuality than do females.
Testosterone shows positive associations with male-typical sociosexual behavior in nonhuman animals. Yet, it remains unclear whether the human sex difference in sociosexual psychology attitudes and desires is mediated by testosterone, whether any relationships between testosterone and sociosexuality differ between men and women, and what the nature of these possible relationships might be.
In studies to resolve these questions, we examined relationships between salivary testosterone concentrations and sociosexual psychology and behavior in men and women. We measured testosterone in all men in our sample, but only in those women taking oral contraception OC-using women in order to reduce the influence of ovulatory cycle variation in ovarian hormone production.
We found that OC-using women did not differ from normally-ovulating women in sociosexual psychology or behavior, but that circulating testosterone mediated the sex difference in human sociosexuality and predicted sociosexual psychology in men but not OC-using women.
Moreover, when sociosexual psychology was controlled, men’s sociosexual behavior number of sexual partners was negatively related to testosterone, suggesting that testosterone drives sociosexual psychology in men and is inhibited when those desires are fulfilled. This more complex relationship between androgens and male sexuality may reconcile some conflicting prior reports. Hypogonadism and erectile dysfunction: an overview. Additionally, changes in mood, diminished well being, fatigue, depression and irritability are also associated with androgen insufficiency.
The critical role of androgens on the development, growth, and maintanence of the penis has been widely accepted. Although, the exact effect of androgens on erectile physiology still remains undetermined, recent experimental studies have broaden our understanding about the relationship between androgens and erectile function.
Preclinical studies showed that androgen deprivation leads to penile tissue atrophy and alterations in the nerve structures of the penis. On the light of the recent literature, we aimed to present the direct effect of androgens on the structures, development and maintanence of penile tissue and erectile physiology as well.
Furhermore, according to the clinical studies we conclude the aetiology, pathophysiology, prevalance, diagnosis and treatment options of hypogonadism in aging men. The medial preoptic area mPOA is a key site for the dopaminergic enhancement of male sexual behavior.
Dopamine release increases in the rat mPOA with mating, supporting the critical stimulatory role played by preoptic dopamine on male sexual behavior. However, it has been questioned whether dopamine is specifically related to the occurrence of male sexual behavior and not simply involved in general arousal. To address this question, we ask whether dopamine release in the mPOA is linked to the production of male sexual behavior in Japanese quail, a species that exhibits a much shorter temporal pattern of copulation than rats and does not have an intromittent organ, resulting in a very different topography of their sexual response.
Extracellular samples from the mPOA of adult sexually experienced male quail were collected every six minutes before, during, and after exposure to a female using in vivo microdialysis and analyzed using HPLC-EC. Extracellular dopamine significantly increased in the presence of a female and returned to baseline after removal of the female.
However, subjects who failed to copulate did not display this increased release. These findings indicate that it is not solely the presence of a female that drives dopamine release in males, but how a male responds to her. Further, in subjects that copulated, dopamine release did not change in samples collected during periods of no copulation. Together, these findings support the hypothesis that dopamine action in the mPOA is specifically linked to sexual motivation and not only copulatory behavior or physical arousal.
The medial preoptic area mPOA is hypothesized to focus the male’s motivation on sexually relevant stimuli, coordinate genital reflexes necessary for erection and ejaculation, and enhance male-typical motor patterns of copulation Hull et al. Based primarily on pharmacological findings, the catecholamine neurotransmitter dopamine DA appears to facilitate male sexual behavior in rats and other mammals partly through its action in the mPOA for a review, see Hull et al.
For example, in rats, DA agonists microinjected into the mPOA facilitate sexual behavior Hull et al. One critical argument in favor of the involvement of DA in the control of sexual behavior is provided by the assessment of DA release during sexual interactions.
In rats, it has been shown that the presence of an estrus female enhances extracellular DA in the mPOA Hull et al. Males that exhibited a substantial precopulatory increase in DA in the mPOA copulated with females, but in the absence of this rise in DA they did not Hull et al. These data thus support the hypothesis that a rise in DA in the mPOA is specifically related to the occurrence of male sexual behavior.
Investigations of DA release in relation to male sexual behavior in the mPOA have been limited to rodents. Quail exhibit robust male sexual behaviors but display a faster temporal sequence as compared to rats. Importantly, they lack an intromittent organ, so the topography of sexual behavior is quite different from mammals. Because quail do not exhibit erections, the detection of a change in the release of DA in the mPOA can not be attributed solely to a change in arousal that might facilitate penile erections but rather such changes can be more readily tied to sexual motivation and performance.
Therefore studies using quail are important to better understand the role of DA release in the mPOA for the control of male sexual behavior. The current report is the first reported case examining whether DA levels, as measured by in vivo microdialysis in the mPOA in quail, is linked to the expression of sexual behavior specifically.
All male quail were deeply anesthetized with isoflurane gas anesthetic IsoSol isoflurane from Vedco. The skull was drilled at the level of the inter-parietal suture. An obturator, cut the same length as the guide cannula, was inserted into the guide cannula until microdialysis experiments began. Joseph, MO, USA was administered for three days following the surgery to reduce pain and inflammation. A Teflon-covered tether encased the inflow tubing.
Nine males were used in the pilot study conducted to identify an appropriate flow rate in which to perform the experiment. Three of the nine animals in this pilot study had inadequate dialysate volume for analysis so their samples were excluded. All birds exhibited copulatory behavior the day prior to testing. Also on the day prior to testing, the birds were placed in the microdialysis chamber without a female for one hour to allow the birds to habituate to the chamber.
On the day of testing, the probe was implanted, the subject was placed in the microdialysis chamber, and the probe was then attached to the perfusion line. Six hours later, three baseline BL samples were collected. The female was then placed into the chamber, where they could copulate.
During this period, six additional samples were collected FEMALE period and the frequency of the consummatory behavior of the birds was recorded. After the last sample was collected, the female was removed and three final samples were collected POST period.
At the conclusion of the experiment, cannula placements were verified histologically. Animals were anesthetized with isoflurane gas anesthetic, and, using the same probe that was used for microdialysis, a dye solution was reverse-dialyzed into the mPOA.
Sections including the mPOA were mounted on slides and examined for cannula placement. No lesions of the mPOA were discovered. All birds were housed, manipulated, and euthanized by using procedures approved by the IACUC at Johns Hopkins University. Data were collected using a PC, running Gilson Medical Electronics Unipoint system controller software, which also controlled the pump parameters.
The mean of the three baseline samples were used as the baseline measure and all values were converted to percentage of baseline.
Non-Copulators as the independent factor. Post-hoc analyses revealed that this change was significantly higher in FEMALE samples compared with baseline. Further, although all subjects copulated in the pretests following the surgery, not all subjects copulated in the microdialysis setting six quail copulated [Copulators] while four did not [Non-copulators] thus making it possible to compare the effect of copulation between variable on the concentration of DA in the preoptic area.
Additionally, among the six males who copulated, four birds provided both COP and NO COP samples refer to Methods for a description. Finally, two animals were found to have cannulae placement outside the mPOA and were thus removed from analysis.
Interestingly, the data from these two birds showed no change in DA release from baseline, suggesting the regional specificity of the DA response. This study represents the first attempt at performing in vivo microdialysis in the mPOA investigating extracellular DA release during male sexual behavior in any species other than in rodents. Our first challenge was to identify an appropriate flow rate in which to perform these experiments. Hence, in the presence of a female, the elevated DA concentration persists regardless of the behavioral response of the male.
Specifically, all birds were exposed to the female, but only the males who eventually engaged in copulation showed the significant rise in DA. Thus, it is not sufficient for the male to see a female, but rather it is whether or not he will eventually respond to her that correlates with this DA response in the mPOA. These data are consistent with the conclusion that DA release in the mPOA is specifically linked to sexual motivation.
These connections support its role as an integrative center for coordinating sexual motivation with its appropriate behavioral output. As is the case in rats, these data indicate that the rise in mPOA DA occurs in the presence of a female only if the male successfully copulates Hull et al. Also similar to what has been observed in rats, removal of the female leads to a rapid decrease in DA release. In the study by Hull et al. Precopulatory levels were collected in the presence of a female where the male could see, hear, and smell her, but could not interact physically with her.
If the male exhibited a rise in DA in the mPOA in response to the female he would then be able to go on and copulate. If he did show this precopulatory rise, he did not engage in copulation. In our current study, we did not collect a similar precopulatory measure. We uncovered no differences in the release of DA during periods in which the male quail is copulating and in the presence of the female as compared to when a female is still present but the male is not copulating.
In addition to the hypothesized actions on sexual motivation, some actions of DA in the mPOA of rats appear to be related directly to the facilitation of penile erections for a review, see Hull et al. Because quail lack an intromittent organ but still exhibit a robust pattern of sexual motivation, quail are a useful model for studying different components of sexual behavior.
In the present experiment, DA levels increases in males who copulated, but contrary to rodents, quail do not need an erection to successfully perform the behavioral sequence. Thus, the DA rise occurs in the absence of the need of erection, further supporting a role of DA in the control of male sexual behavior rather than only erection and ejaculation.
Thus, in quail and in rats, DA can both inhibit and facilitate male sexual behavior. However, given the differences in the topography of male-typical sexual behavior in rats versus quail, while the release of DA in the mPOA occurs in the presence of a female in both species, the functional consequences of DA changes may vary between the species.
For example, in rats, DA in the mPOA is thought to play a role in the control of erections and ejaculation as well as a role in sexual motivation. We have observed in male quail who will engage in copulation a pattern of mPOA DA release in the presence of a female similar to that observed in rats.
In particular in this current study, we compared DA levels in male quail that were in the presence of female and either engaged or did not engage in copulatory behavior. A novel finding of our study is that in birds that either had or eventually would copulate, DA was high in the presence of a female even during sampling periods when they were not copulating.
These findings support a role of DA release in the control of sexual motivation in quail. In summary, the results from the current experiment suggest that consummatory behavior per se does not modulate the release of DA in the mPOA.
Rather, when the male is motivated and able to copulate, it is the presence of a female that appears to correlate with an increase in DA levels. Specifically, we observed a rise in DA only in subjects who copulated, but this was not strictly correlated with the performance of the behavior, suggesting a link to motivation. They argue that the effects of DA manipulations on male sexual functioning can be explained via the modulation of general arousal or motoric function rather than a specific role on sexual behavior.
However, the present experiment shows that the rise in DA occurs in quail, a species that has no need for an erection, linking the release of DA in the mPOA to sexual behavior and not solely physical arousal. Overall, these data are consistent with the notion that DA in the mPOA is specifically linked to sexual motivation.
CAC is an F. In addition, we thank Zachary Hurwitz for helping inject samples in the HPLC-EC and Jim Garmon for his assistance building the testing chambers.
Publisher’s Disclaimer: The following manuscript is the final accepted manuscript. It has not been subjected to the final copyediting, fact-checking, and proofreading required for formal publication. It is not the definitive, publisher-authenticated version.
The American Psychological Association and its Council of Editors disclaim any responsibility or liabilities for errors or omissions of this manuscript version, any version derived from this manuscript by NIH, or other third parties. Anabolic-androgenic steroid AAS abuse is widespread.
Moreover, AAS are reinforcing, as shown by self-administration in rodents. However, the receptors that transduce the reinforcing effects of AAS are unclear. AAS may bind to classical nuclear androgen receptors ARs or membrane receptors. We used two approaches to examine the role of nuclear ARs in AAS self-administration. First, we tested androgen self-administration in rats with the testicular feminization mutation Tfmwhich interferes with androgen binding. If nuclear ARs are essential for AAS self-administration, Tfm males should not self-administer androgens.
Taken together, these data demonstrate that nuclear ARs are not required for androgen self-administration. Furthermore, androgen self-administration may be mediated by plasma membrane receptors. Anabolic-androgenic steroids AAS are drugs of abuse.
These testosterone T derivatives are used for athletic and aesthetic purposes Yesalis et al. Despite growing concerns, the underlying mechanisms of AAS abuse have not been well-understood. Evidence from animal research supports this hypothesis. AAS induce conditioned place preference CPP in mice Arnedo et al. While ICV self-administration suggests central sites of action, the specific hormones and receptors mediating AAS reinforcement are unclear.
Current evidence suggests that the reinforcing effects of T are mediated by androgens, rather than through estrogens after aromatization. The question now becomes: how is the androgenic signal transduced in the brain?
The androgen receptor AR is a classic nuclear steroid receptor which functions as a transcription factor. There is also evidence for gonadal steroids acting via cell surface receptors Mermelstein et al.
In the current study, we used two approaches to determine the role of classic nuclear AR in androgen reinforcement. To minimize possible activation of estrogen receptors ERwe tested DHT self-administration.
In the first experiment, rats with the testicular feminization mutation Tfm were tested for ICV self-administration of DHT. Tfm is a single base substitution which results in defective ARs with limited ligand binding Yarbrough et al. Male Tfm rats exhibit an external female phenotype due to insufficient androgenic stimulation during development Zuloaga et al. If functional nuclear ARs are required for AAS reinforcement, Tfm rats should not self-administer DHT.
Instead, Tfm rats were able to acquire DHT self-administration. In the second experiment, we tested ICV self-administration of membrane-impermeable forms of DHT in hamsters.
When DHT is conjugated to bovine serum albumin BSAits actions are restricted to cell-surface receptors. If nuclear ARs are required for androgen reinforcement, hamsters should not self-administer DHT conjugated to BSA.
On the contrary, the hamsters showed a clear preference for DHT conjugated to BSA. Together, these studies show that nuclear ARs are not required for androgen self-administration. Instead, androgen reinforcement may be mediated by membrane ARs. Adult male Tfm rats and wild-type WT littermates were obtained from a colony at Michigan State University. Their genotype was verified by PCR, similar to methods described previously Fernandez et al.
Tfm animals were also verified by phenotype, by the presence of nipples, feminine ano-genital distance and abdominal testes. Tfm rats have previously been used to demonstrate non-genomic androgen effects in hippocampus MacLusky et al. Animals were allowed to recover for at least a week following the surgery before testing.
DHT, DHT-carboxymethyl-oxime CMODHT-CMO-BSA, DHT-hemisuccinate Hemisand DHT-Hemis-BSA were obtained from Steraloids Newport, RI. Both DHT-CMO-BSA Gatson et al. Previous studies have shown that only a small proportion of steroid dissociates from BSA Stevis et al. Albans, VT enclosed in a sound-attenuating chamber with forced ventilation. The tubing connecting the swivel and the ICV cannula was protected by a metal spring.
One of the nose-poke holes was designated as the active nose-poke hole. A response on the other nose-poke hole was recorded as an inactive nose-poke I but did not result in any infusion.
The location of the active nose-poke hole to the front or the back of the chamber was balanced to control for side preferences. The data were recorded by WMPC software Med Associate on a Windows PC. Additionally, the average number of reinforcements per session for each animal at each FR was compared.
In those cases, only the data from the completed schedules were included in the analyses. A three-way ANOVA was followed up by appropriate lower order ANOVAs for simple effects. The Newman-Keuls test for post-hoc pair-wise comparisons was used when necessary. The individual means of R, NR, and I were used for data analysis. Additionally, the number of reinforcements received was averaged for each animal. There was no main effect of genotype, and other interactions were not significant.
The average number of DHT and Veh infusions received at each FR is shown in Fig. All other interactions and main effects were not significant. There was no effect of drug condition DHT v. Hamsters self-administered DHT and DHT conjugated to BSA, but not BSA alone. The number of infusions received for each group is shown in Fig.
As with testosterone overdose, none of the hamsters in the present study died during self-administration. Instead, hamsters died several hours later in their home cages, with severe locomotor and respiratory depression. The current study demonstrates that classical nuclear ARs are not essential for androgen self-administration.
Both Tfm and WT rats developed a preference for the active nose-poke during DHT self-administration. Furthermore, they were able to respond to the ascending FR schedule by increasing active nose-pokes, thereby maintaining a steady level of drug intake regardless of the FR schedule. In contrast, rats receiving vehicle failed to respond to the changes in the FR schedule. Their active nose-pokes did not significantly increase in response to changes in FR schedule, and they received fewer infusions as the response requirement increased.
The unexpectedly high responding for vehicle by Tfm rats is unlikely to be due to the vehicle itself. We observed similar phenomena in a separate group of Tfm rats who were not receiving any infusions data not shown.
Instead, it may be related to feminized behavioral traits in the Tfm males. Alternatively, the Tfm rats and mice are known to exhibit heightened anxiety-like behaviors Zuloaga et al. In addition, self-administration of DHT-BSA conjugates in male hamsters provides evidence that androgens may act at the neuronal plasma membrane to have reinforcing action. Hamsters exhibited a significant preference for both DHT-BSA conjugates. In contrast, hamsters showed no preference for BSA alone.
The current study reveals a species-specific pattern of operant responding. In rats, however, there was a clear preference for active nose-poke regardless of the drug received. We observed a similar trend in our previous study on IV self-administration of T in rats, although it was not statistically significant Wood et al. Based on such species-specific behavioral difference in self-administration, a caution must be taken when comparing behavioral data from rats and hamsters.
There are several caveats that need to be considered in interpretation of the current study. First, nuclear ARs with significantly impaired ligand binding are still present in Tfm rats Yarbrough et al. It is possible that these mutated nuclear ARs are sufficient for mediating effects of androgens at supra-physiological doses.
Second, the DHT-BSA conjugates may degrade in vivoresulting in free DHT. Finally, DHT-BSA conjugates may not significantly penetrate into the brain tissue. DHT-BSA is significantly larger than DHT, thus the effects of DHT-BSA observed in the current study are likely to be mediated at sites close to the ventricles. Despite these caveats, these two different approaches produced consistent results which argue strongly against the necessity for nuclear AR in androgen reinforcement.
In addition, the self-administration of BSA conjugates suggests that androgens may act at the plasma membrane in androgen reinforcement. To our knowledge, the current study provides the first in vivo evidence for behaviorally relevant effects of androgens at the plasma membrane.
Several other studies on androgen reward have shown results consistent with non-genomic or plasma membrane effects. CPP can be also induced with intra-Acb infusions of T or its metabolite Packard et al. The current study does not provide information regarding the site of action in the brain. Nonetheless, it does indicate that the relative lack of nuclear AR alone is not a sufficient reason to exclude structures such as Acb and VTA from the potential sites that may mediate androgenic effects.
Rapid plasma membrane effects of steroids in dorsal and ventral striatum are not limited to androgens. Estrogens also exert rapid, membrane receptor-mediated effects in the dorsal striatum Mermelstein et al. A membrane-associated receptor has already been isolated for progestins Zhu et al. Historically, the effects of steroids, including androgens, were considered to be transduced by nuclear receptor-mediated processes.
However, reports of rapid androgen effects, presumably mediated by membrane-associated receptors, have been available for several decades. The cell types with possible membrane ARs include glial Gatson et al.
Although the molecular identity has yet to be determined, candidates for the membrane AR include membrane receptors with known steroid binding sites, such as GABA-A reviewed in Lambert et al. In addition, the effects of androgens unrelated to a specific receptor cannot be excluded in the current study. Recent in vitro studies suggest that there are multiple membrane ARs, or more than one binding site on a single receptor, as proposed for the membrane progesterone receptor Ramirez et al.
However, the steroid binding characteristics and the sensitivity to anti-androgens of the putative membrane AR vary greatly depending on the cell type. Further research is required to elucidate the characteristics of androgens self-administered.
Given such wide-spread use, AAS abuse has wide-ranging health consequences. These and the anabolic effects of AAS have been thought to be mediated through nuclear AR. However, the possible nuclear AR-independent effects of androgens suggest that the influence of AAS may extend well beyond structures with nuclear AR expression.
As far as resemblance to other drugs of abuse, AAS produce different effects and have different mechanisms of action from stimulants. Unlike stimulants Graybiel et al. Furthermore, AAS attenuate stimulant-induced Acb DA release Birgner et al. Instead, behavioral responses to acute AAS resemble those of opioids or benzodiazepines, possibly exerting additive effects when taken together. Furthermore, nandrolone, a commonly-used AAS, potentiates hypothermic effects of morphine and exacerbate naloxone-precipitated morphine withdrawal symptoms Celerier et al.
Increased ethanol consumption in rats chronically treated with AAS may also be an reflection of altered GABAergic function Johansson et al. Our findings on overdose raise an additional health concern. However, the current study demonstrates that the anabolic efficacy of AAS does not necessarily correspond to their reinforcing properties and overdose risks. In light of these findings, the criteria used for scheduling a steroid as a controlled substance may require revisions to account for its abuse liability and toxicity, in addition to its anabolic potency.
The results of the current study suggest that nuclear AR, the only AR isolated so far, is not essential for the androgen reinforcement. Instead, the results suggest that androgen reinforcement is transduced at the plasma membrane. Thus, further inquiries into the identity of putative membrane AR, their functional characteristics and anatomical distribution are required to elucidate the underlying mechanism of AAS abuse and its clinical implications.
COMMENTS: Study reveals the nucleus accumbens as the center of the sexual universe. This mall but powerful structure governs all rewards and transition to an addicted state. To investigate this issue, we recorded single unit activities in the NAc shell of male rats during sexual behavior. The two types of NAc shell neurons [putative fast spiking interneurons pFSIs and medium spiny neurons pMSNs ] responded differently during sexual behavior. First, more pFSIs than pMSNs exhibited inhibitory responses to thrusting with intromission and genital grooming, while pFSIs and pMSNs responded similarly to sniffing of females.
Furthermore, NAc shell neuronal activity was significantly different across the different phases of sexual behavior, and the number of NAc shell neurons with delta oscillation, which is related to behavioral inhibition, and high gamma oscillation, which is related to reward perception, increased after ejaculation.
Together, our results suggest that the NAc shell is deeply involved in sexual behavior, and changes in NAc shell neuronal activity are related to performance of sexual behavior, encoding cues or contexts related to sexual behavior, reward-related processing, and the inhibition of sexual behavior after ejaculation. Dopamine and the sex hormone testosterone are important factors regulating male sexual behavior.
To investigate the possibility that these two factors are functionally interrelated, we investigated the potential role of the androgen receptor AR on transcriptional activity of the tyrosine hydroxylase TH gene that encodes the rate-limiting enzyme of the dopamine biosynthesis pathway. No hormone was injected prior to the test session. The findings indicate that intra- accumbens injections of testosterone are sufficient to produce reward. The decline of testosterone has been known to be associated with the prevalence of erectile dysfunction EDbut the causal relationship between sex hormones and ED is still uncertain.
To prove the association between sex hormones and ED, we carried out a prospective cohort study based on our previous cross-sectional study. High FT and BT levels independently predicted a decreased risk of ED in young men. Further studies are urgently needed to clarify the molecular mechanisms of testosterone acting on ED. Luo Y, Zhang H, Liao M, Tang Q, Huang Y, Xie J, Tang Y, Tan A, Gao Y, Lu Z, Yao Z, Jiang Y, Lin X, Wu C, Yang X, and Mo Z. Sex hormones predict the incidence of erectile dysfunction: From a population-based prospective cohort study FAMHES.
He pioneered the use of microdialysis, and also effectively used electrical stimulation, lesions, microinjections, and immunohistochemistry. He found that feeding, stimulant drug administration, and electrical stimulation of the lateral hypothalamus LH all increased dopamine DA release in the nucleus accumbens NAc. However, whereas DA in the NAc enhanced motivation, DA in the LH inhibited motivated behaviors.
The Hull lab has pursued some of those ideas. We have shown that DA release in the medial preoptic area MPOA is very important for male sexual behavior, and that testosterone, glutamate, nitric oxide NO and previous sexual experience promote MPOA DA release and mating. Bart Hoebel is a giant among neuroscientists. He pioneered new techniques and produced seminal insights into the workings of the brain. His use of microdialysis and high performance liquid chromatography HPLC to collect and analyze neurotransmitters in various brain areas provided important concepts about the interactions between the hypothalamus and the mesocorticolimbic dopamine DA system.
Much of my own work has been along the paths that he established. A second Science article extended his study of motivated behaviors to include copulation. Furthermore, there were unexpected interactions among brain areas.
For example, there was an inverse relation between the effects of DA in the lateral hypothalamus LH vs. DA in the LH was unpleasant and inhibited motivated behaviors, but DA in the NAc was rewarding and promoted motivated behaviors. My lab has followed up on some of these ideas. We have used microdialysis, microinjection, and immunohistochemistry, together with behavioral testing, to probe the circuitry mediating male rat sexual behavior.
A group of neurons in the LH produces the peptide orexin OX, also known as hypocretin, HCRT. The two lower doses increased cell firing and population responses, although the highest dose apparently resulted in depolarization block of VTA dopaminergic neurons, which was reversed by stimulating DA autoreceptors with the DA agonist apomorphine. In addition to the LH and mesocorticolimbic DA system, my lab has investigated the role of the MPOA, at the anterior end of the hypothalamus, in the control of male sexual behavior.
Electrical or chemical stimulation of the MPOA enhances copulation and ex copula genital reflexes. There is a close correlation between male rat sexual behavior and extracellular DA levels in the MPOA. The recent presence of testosterone was necessary for both DA release and copulation. Oil-treated castrates that did not copulate did not show the increase. There was both behavioral and anatomical specificity for the DA response.
Furthermore, the fact that DA increased before mating began suggests that the increase was not caused by copulation, but was probably associated with sexual motivation.
Testosterone treatment for two days did not restore mating or the DA response. Most of the five-day testosterone-treated castrates were able to copulate and showed a DA response, with half of them able to ejaculate. There were again numerous correlations between copulatory measures and DA levels. Therefore, both the loss of copulation following castration and its restoration by testosterone are closely associated with the MPOA DA response to an estrous female.
Testosterone-mediated enhancement of sexual activity may occur in part through increased DA release in the MPOA. Gonadally intact male rats showed an increase in extracellular DA during precopulatory exposure to an inaccessible estrous female, and all intact males then copulated when the female was placed in their cage.
Estradiol restored normal basal levels of DA, but not the increase in response to a female. Estradiol-treated castrates intromitted, but none showed an ejaculatory behavior pattern. Neither dihydrotestosterone nor oil vehicle maintained copulation or basal or female-stimulated DA release. Therefore, we tested whether NO would have similar effects in the MPOA. Therefore, one means by which testosterone facilitates copulation is by increasing nNOS in the MPOA, which in turn increases both basal and female-stimulated DA release in intact males and testosterone-treated castrates.
Our lab has also investigated the effects of sexual experience. NO may mediate some of the cellular effects of experience. When administered into the MPOA before each of seven exposures to an estrous female, it blocked the facilitative effects of those exposures. Therefore, increases in NO production in the MPOA, and its consequent increase in DA release, may mediate some of the beneficial effects of sexual experience.
A major stimulus for the MPOA DA response to a female is input from the medial amygdala MeA. However, microinjections of the DA agonist apomorphine into the MPOA completely restored copulation in those males. Smaller radiofreqency lesions of the MeA impaired, but did not abolish copulation. Therefore, one way in which the MeA promotes copulation is by increasing DA release in the MPOA. Lesions of the medial amygdala inhibit the release of DA in the MPOA resulting from exposure to an estrous female and copulation.
Extracellular DA significantly increased during the precopulatory and copulatory stages of testing for animals with sham lesions but not for animals with MeA lesions. Levels of DA in dialysate from the MPOA of animals receiving MeA stimulation or vehicle microinjection.
Levels of extracellular DA significantly increased after MeA microinjections for animals receiving MeA stimulation but not for animals receiving vehicle. Reverse dialysis of glutamate reuptake inhibitors increased extracellular glutamate, as expected, and also facilitated copulation. The nNOS inhibitor L-NAME, when reverse-dialyzed into the MPOA, decreased baseline DA and blocked the glutamate-evoked DA release.
The inactive isomer D-NAME had no effect. Glutamate binds to NMDA receptors to promote calcium influx, which activates calmodulin, which in turn activates nNOS. Therefore, glutamate, through its stimulation of nNOS, increases DA release in the MPOA, which in turn facilitates copulation. MPOA glutamate may also help to elicit ejaculation. Using electrical stimulation, lesions, microinjections, microdialysis, and immunohistochemistry, as well as careful and systematic behavioral observation, he mapped the brain areas and neurotransmitters that control feeding, mating, aggression, drug intake, and reward.
The Hull lab has followed up on some of those ideas, including the interaction between the LH and the mesocorticolimbic DA system. We have studied primarily male sexual behavior, showing that testosterone and sexual experience increase nNOS in the MPOA, and that the resultant increase in NO production would increase both basal and female-stimulated DA release.
Furthermore, glutamate is also released in the MPOA during mating, especially at the time of ejaculation, and glutamate, acting via NMDA receptors and calcium inflow, may increase NO, and thereby DA release. It is a great pleasure to know, interact with, and learn from him. Both estradiol E and dihydrotestosterone DHT contribute to the activation of mating, although E is more important for copulation and DHT, for genital reflexes.
Hormonal activation of the medial preoptic area MPOA is most effective, although implants in the medial amygdala MeA can also stimulate mounting in castrates. Chemosensory inputs from the main and accessory olfactory systems are the most important stimuli for mating in rodents, especially in hamsters, although genitosensory input also contributes.
Norepinephrine agonists and opiates have dose-dependent effects, with low doses facilitating and high doses inhibiting behavior. Keywords: Rats, mice, hamsters, guinea pigs, estradiol, dihydrotestosterone, testosterone, medial preoptic area, medial amygdala, genital reflexes Reproductive behaviors and their neural and hormonal regulation vary widely across species. Yet much research has focused on relatively few animals.
We describe the behaviors of male rodents and their neural, hormonal, and experiential regulation. We begin with rats, the most common subjects of laboratory research. We then describe the behaviors of male mice, hamsters, and guinea pigs, noting similarities and differences among species.
Because of the vast amount of research on rodents, and the page limits for this manuscript, we can cite only a small portion of it. For additional details, please consult Hull et al.
He then springs backward rapidly and grooms his genitals. It is accompanied by rhythmic contractions of the bulbospongiosus and ischiocavernosus muscles at the base of the penis, and of anal sphincter and skeletal muscles Holmes et al. Aging male rats lose the ability to ejaculate, which is not restored by exogenous T Chambers et al. A decline in estrogen receptors ER Roselli et al.
Ex copula reflexes can be observed in several contexts. Spontaneous or drug-induced erections occur in the home cage or neutral arena. Volatile odors from an estrous female elicit noncontact erections, which may be a model for psychogenic erections in humans.
These erections result from engorgement of the corpus spongiosum, which produces tumescence of the glans penis reviewed in Hull et al. Occasionally, seminal emission occurs in this context. The continuing pressure of the retracted sheath around the base of the penis provides the stimulus for these touch-based reflexes. Finally, the urethrogenital reflex has been studied in anesthetized male and female rats as a model of orgasm in humans McKenna et al.
Therefore, rapid, probably membrane-based, hormonal effects may contribute to sexual motivation, but longer-term genomic effects are required for full restoration of mating. DHT, which is nonaromatizable and has greater affinity for ARs than does T, is ineffective when administered alone. Thus, androgens contribute to motivation and performance and are also necessary and sufficient to maintain ex copula genital reflexes Cooke et al. Transmitters often act synergistically in multiple sites, and the site of action often is not known a priori.
Therefore, systemic drug administration can be useful. Chemosensory input from the main and vomeronasal systems is probably the most important stimulus for male rodent sexual behavior. Information from the main and accessory olfactory systems is processed in the medial amygdala MeAalong with somatosensory input from the genitals, relayed through the parvocellular portion of the subparafascicular nucleus SPFpwhich is also part of an ejaculation circuit in several species reviewed in Hull et al.
The MPOA is arguably the most critical site for orchestrating male sexual behavior. Many studies have reported severe and long-lasting impairment of copulation following lesions of the MPOA reviewed in Hull et al.
However, male rats with MPOA lesions continued to show noncontact erections Liu et al. Conversely, stimulation of the MPOA facilitated copulation, but did not elicit mating in sated males Rodriguez-Manzo et al. Stimulation also increased intracavernosal pressure in anesthetized males Giuliano et al. MPOA apomorphine also restored copulation in males with large amygdala lesions Dominguez et al.
These effects were anatomically and behaviorally specific. DA is released in the MPOA before and during copulation Hull et al. Again, there was both behavioral and anatomical specificity. Recent, but not concurrent, T was necessary for the DA increase and copulation Hull et al.
Input from the MeA is required for the DA response to a female, but not for basal DA levels Dominguez et al. Reverse-dialysis of glutamate into the MPOA increased DA release, an effect blocked by a NOS inhibitor Dominguez et al.
Similarly, glutamate microinjected into the MPOA increased intracavernous pressure Giuliano et al. Therefore, a consistent picture emerges, in which glutamate, at least in part from the MeA and BNST, facilitates copulation and genital reflexes, both directly and via NO-mediated increases in DA, which also contributes to the initiation and progress of copulation.
Low levels of opioids may facilitate, and higher doses inhibit copulation reviewed in Hull et al. Electrophysiological recordings revealed that different MPOA neurons contribute to sexual motivation and copulatory performance Shimura et al.
Mating increases Fos-ir in the MPOA reviewed in Hull et al. Therefore, sexual experience may enhance the processing of sexually relevant stimuli. The mesocorticolimbic DA tract, ascending from the ventral tegmental area VTA to the nucleus accumbens NAc and prefrontal cortex, is important for reinforcement and appetitive behaviors.
VTA or NAc lesions increased PEIs and decreased noncontact erections, but did not affect copulation reviewed in Hull et al. Applications of drugs to the VTA or NAc primarily affected general activation, rather than specifically sexual behavior reviewed in Hull et al.
The paraventricular nucleus PVN of the hypothalamus comprises a magnocellular division, which releases oxytocin and vasopressin into the circulation from the posterior pituitary, and a parvocellular division, which projects to several brain areas and the spinal cord.
Excitotoxic lesions of the parvocellular portion decreased noncontact erections but did not impair copulation Liu et al. Similar lesions decreased the amount of semen ejaculated and the number of oxytocin-containing fibers in the spinal cord, but again did not affect copulation Ackerman et al.
Lesions that encompassed both divisions did impair copulation, as well as touch-based and noncontact erections Liu et al. Argiolas and Melis have provided an elegant picture in which DA, oxytocin, and glutamate Melis et al. GABA and opioids inhibit these processes. This lab has also shown that DA Melis et al. Several additional brain areas influence male rat sexual behavior. Therefore, this may be one site at which SSRI antidepressants act to inhibit sexual function.
The nucleus paragigantocellularis nPGi of the medulla is a major source of inhibition of male rat sexual behavior. Lesions facilitated copulation and delayed sexual satiety Yells et al. Similar lesions facilitated touch-based reflexes Holmes et al.
The mouse has become popular for behavioral studies, largely because of our ability to generate transgenics, knockouts, and knockdowns see Burns-Cusato et al. There are many strain differences in mouse mating. In place preference tests both intromissions and ejaculations were shown to be rewarding Kudwa et al. Touch-based reflexes have also been observed in mice. However, additional implants of T in the VTA, which were ineffective alone, produced synergistic effects on mounting and urine preference.
The testicular feminization Tfm, or androgen insensitivity mutation in mice, as well as other animals, results from deletion of a single base in the AR gene reviewed in Burns-Cusato et al. Tfm males appear phenotypically female, are infertile, and engage in no sexual behavior if tested without exogenous hormones. Small testes secrete low levels of T and DHT. However, apomorphine icv restored only mounts and intromissions described in Burns-Cusato et al. Males lacking both ERs did not copulate at all when gonadally intact Ogawa et al.
Males lacking aromatase ArKO are unable to synthesize E but have normal receptors. Chemosensory cues are extremely important for sexual behavior in male mice reviewed in Hull et al.
However, the vomeronasal system may have an important, but not critical, role in mating. MPOA lesions severely impaired copulation in male mice, as in other species reviewed in Hull et al. The female Syrian golden hamster remains in a lordosis posture continuously through successive copulations.
The duration of penile insertion was longer in ejaculations than in intromissions, but was shorter in than in long intromissions. Lack of T during puberty impaired copulation after T replacement in adulthood, compared with castrates with T replacement during puberty Schultz et al.
Repeated sexual experiences did not compensate for these deficits. The odor of a receptive female activated Fos-ir in the MPOA even before puberty Romeo et al. Therefore, puberty may be a second organizational period in which gonadal hormones permanently alter neural processing in areas that regulate sexual behavior Romeo et al.
Bilateral olfactory bulbectomy or combined deafferentation of the main and accessory olfactory systems permanently abolished sexual behavior reviewed in Hull et al. Mating-induced increases in Fos-ir in the main and accessory olfactory bulbs were specific to chemosensory stimuli, rather than to mating reviewed in Hull et al.
Thus, hormonal activation of the MeA is sufficient for expression of sexual behavior in male hamsters. Projections from the MeA travel via the stria terminalis and ventral amygdalofugal pathway to the BNST, MPOA, and other areas. Cutting the stria terminalis delayed and slowed copulation, and combined cuts of both pathways eliminated copulation Lehman et al.
As with many other species, the MPOA is critical for sexual behavior in male hamsters. Although there are differences in the copulatory elements among rodents, the hormonal factors and neural circuitry that control those elements are similar.
Both E and DHT contribute to the activation of mating, although E is more important for copulation and DHT, for genital reflexes of rats, mice and hamsters. Hormonal activation of the MPOA is most effective, although implants in the MeA can also stimulate mounting in castrates.
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Morphine inhibits dopaminergic and cholinergic induced ejaculation in rats. However, there is little information regarding the rewarding values of the different components of sexual behavior.
Therefore, this study used a conditioned place preference CPP paradigm to address whether ejaculation and intromissions differ in their rewarding incentive values. We also addressed whether the differential rewarding values were dependent on prior sexual experience.
The amount of time spent in each chamber of the CPP apparatus after conditioning was then measured. These data support the hypothesis that there is a hierarchy of rewarding sexual behavior, with ejaculation being the most rewarding component, and that the rewarding incentive value of other components of sexual behavior is dependent upon prior sexual experience. Keywords: reward, conditioned place preference, copulation, sexual behavior, associative learning In male rodents, sexual behavior is a rewarding and reinforcing behavior, composed of various elements, including anogenital investigation, mounts, intromissions, and ejaculation.
Ejaculation appears to be the most reinforcing component of sexual behavior Coolen et al. In addition, ejaculation is essential for the formation of conditioned copulatory preferences. The CPP paradigm measures approach responses to environmental stimuli that previously have been paired with reinforcing events and can be used to evaluate the incentive value of these rewarding events and the reward-related stimuli Carr et al.
The apparatus used to demonstrate CPP typically consists of distinctive compartments that are paired differentially with unconditional stimuli: one side is paired with copulation to ejaculation, while the other side is paired with nothing or a control manipulation.
However, it is not known whether the development of CPP is dependent on display of ejaculation, or if display of intromissions is sufficient. We hypothesize that ejaculation is more rewarding compared to other elements of sexual behavior given the previous studies showing its greater incentive properties.
Thus, the current set of experiments examined whether ejaculation is more rewarding than the display of multiple intromissions using the CPP paradigm. Moreover, the influence of sexual experience on the rewarding value of intromissions or ejaculation was investigated. Food and water were available at all times except during behavioral testing.
All procedures were approved by the Animal Care and Use Committee of the University of Cincinnati, University of Western Ontario Animal Care Committee, and conformed to NIH and CCAC guidelines involving vertebrate animals in research. Chambers were differentiated by both visual and tactile cues. One test chamber had white walls and metal grid flooring, while the other had black walls and parallel bar flooring. The central compartment consisted of grey walls and a smooth grey floor.
Doors on both sides of the central compartment separated the chambers, and could be raised to allow the animals free movement throughout the apparatus, or lowered to confine them to a particular area. All testing took place in the dark phase three to six hours after lights off. Subjects were videotaped, and time spent in each chamber was analyzed using the Microscoft Excel Custom Macro Program. The chamber in which the animal spent less time the initially non-preferred side was designated the sex-paired side, and the other side the initially preferred side was designated the control side.
Conditioning took place on days two and three. Half the animals in each experiment were given the sex pairing on day two and placed in the control chamber on day three. The remaining animals were given the control pairing on day two and the sex pairing on day three.
Four experiments were performed. Display of ejaculation was determined based on the characteristic motor behavior the animal displays upon ejaculation, as well as the presence of vaginal plug in the female partner. In the second experiment, sexually experienced males were used. These males were mated to one ejaculation in five mating sessions prior to CPP conditioning. Only males that displayed ejaculation in three of these five sessions were included in this experiment.
Half of the males received an ejaculation pairing on the first conditioning day, and half received an intromissions pairing. The pretest and posttest data collected from the sexual behavior CPP experiments were expressed as the preference score the percentage of time spent in the sex-paired chamber and the difference score time spent in the sex-paired chamber minus time spent in the non sex-paired chamber.
Paired t-tests were used to analyze the significance of the preference score and the difference score between the pretest and the posttest. In addition, a Pearson Product Moment Correlation test was used to analyze a possible correlation between the numbers of intromissions and the posttest preference score and difference score within each experiment.
One pairing with display of ejaculation A, B or intromissions C, D induced CPP in sexually naive males. A, C preference score, the percentage of time spent in the ejaculation- A or intromissions- C paired chamber.
B, D difference score, time more. One pairing with display of ejaculation A, Cbut not with intromissions C, D induced CPP in sexually experienced males. B, D difference more. In the third and fourth experiments, the hypothesis that ejaculation is more rewarding compared to intromissions was tested.
Therefore, a fourth experiment was conducted with an extended conditioning period consisting of three of each type of conditioning trial. Thus, with multiple pairings, ejaculation induced the formation of a CPP when compared to display of intromissions without ejaculation.
Therefore, to rule out a positive correlation between the numbers of intromissions and formation of CPP, a correlation analysis was performed. This analysis revealed there were no correlations in any of the experiments between the numbers of intromissions and expression of CPP.
The current study tested the hypotheses that ejaculation has a greater rewarding value compared to display of intromissions when examined using the CPP paradigm and that sexual experience influences the rewarding properties of intromissions. Indeed, it was demonstrated that ejaculation, but not intromissions resulted in the acquisition of CPP in sexually experienced animals. CPP is a well-established paradigm used to study the rewarding properties of sexual behavior Hughes et al.
Two variations in the CPP procedure, postcopulatory CPP and copulatory CPP, differ in whether the mating takes place in the CPP chamber or not Pfaus et al. In the first procedure, which was used in the current study, male rats are allowed to copulate in a separate arena and then transferred immediately to one distinctive compartment of the CPP apparatus.
In the second procedure, copulation to ejaculation is allowed to occur within the CPP chamber itself. Both procedures result in robust and reliable CPP. However, the postcopulatory CPP was used in the present study to eliminate a possible influence of anticipation of sexual reward on the formation of CPP. When male rats are exposed to environmental cues that are associated with prior sexual behavior, the mesolimbic system becomes activated Balfour et al.
The use of a copulatory CPP paradigm will therefore lead to influences of exposure to conditioned cues associated with the prior sexual experience in the CPP chamber.
Another variable in CPP experiments is the number of conditioning trials: Either single Straiko et al. Since one objective of the current study was to investigate the influence of sexual experience on sex-induced CPP, single pairings were utilized for the majority of the experiments in order to prevent reaching a ceiling of mating-induced CPP.