Hormonal regulation of brain circuits mediating male sexual behavior in birds

Male sexual behavior in both field and laboratory settings has been studied in birds since the 19th century. Birds are valuable for the investigation of the neuroendocrine mechanisms of sexual behavior, because their behavior can be studied in the context of a large amount of field data, well-defined neural circuits related to reproductive behavior have been described, and the avian neuroendocrine system exhibits many examples of marked plasticity. As is the case in other taxa, male sexual behavior in birds can be usefully divided into an appetitive phase consisting of variable behaviors (typically searching and courtship) that allow an individual to converge on a functional outcome, copulation (consummatory phase). Based primarily on experimental studies in ring doves and Japanese quail, it has been shown that testosterone of gonadal origin plays an important role in the activation of both of these aspects of male sexual behavior. Furthermore, the conversion of androgens, such as testosterone, in the brain to estrogens, such as 17beta-estradiol, is essential for the full expression of male-typical behaviors. The localization of sex steroid receptors and the enzyme aromatase in the brain, along with lesion, hormone implant and immediate early gene expression studies, has identified many neural sites related to the control of male behavior. The preoptic area (POA) is a key site for the integration of sensory inputs and the initiation of motor outputs. Furthermore, prominent connections between the POA and the periaqueductal gray (PAG) form a node that is regulated by steroid hormones, receive sensory inputs and send efferent projections to the brainstem and spinal cord that activate male sexual behaviors. The sensory inputs regulating avian male sexual responses, in contrast to most mammalian species, are primarily visual and auditory, so a future challenge will be to identify how these senses impinge on the POA-PAG circuit. Similarly, most avian species do not have an intromittent organ, so the projections from the POA-PAG to the brainstem and spinal cord that control sexual reflexes will be of particular interest to contrast with the well characterized rodent system. With this knowledge, general principles about the organization of male sexual circuits can be elucidated, and comparative studies relating known species variation in avian male sexual behaviors to variation in neural systems can be pursued.     

Inactivation of the medial preoptic area/anterior hypothalamus by lidocaine reduces male sexual behavior and sexual incentive motivation in male rats

Permanent bilateral lesions of the medial preoptic area anterior hypothalamus (MPOA/AH) produce a drastic inhibition of male sexual behavior in all species studied to date. The present experiment was designed to evaluate if temporal inactivation of the MPOA/AH by infusions of lidocaine also inhibits sexual behavior in male rats. This would allow us to rule out the possibility that the behavioral effects observed after damage of the MPOA/AH could be associated with plastic changes induced by the lesion in other brain regions. We also evaluated sexual incentive motivation in males after the infusion of lidocaine in a test in which copulation is not possible but where males maintain approach behavior to the estrous females despite repeated testing. The percentage of animals displaying mounts, intromissions and ejaculation was significantly reduced while mount and intromission latency were prolonged after infusion of lidocaine. No changes were observed in sexual behavior after infusion of lidocaine in animals with cannulae outside the MPOA/AH suggesting that the inhibitory effects are specific to this brain region. Sexual incentive motivation was also affected by administration of lidocaine. Males consistently showed a clear preference for the sexually receptive female except when infused with lidocaine. After the infusion of the compound a significant reduction in the time spent in the incentive zone of the stimulus female was observed. These results support the hypothesis that neurons of the MPOA/AH are involved in the control of male sexual motivation.     

Effect of prepuberal medial preoptic area lesions on male rat sexual behavior

Studies have shown that the medial preoptic area (MPOA) is necessary for male sexual behavior in many species. Sparing of function occurs in rats which have MPOA-lesions made prepuberally and are reared in heterosexual group cages. In the present study, male rats with MPOA-lesions made prepuberally and control-operated animals were reared either in group or solitary cages. In three regular mating tests few MPOA-animals reared in isolation displayed sexual behavior, while those reared in groups performed no differently from control animals. Animals with MPOA-lesions that mated exhibited the same frequency and developmental progression of play behaviors as their control peers. In sexual exhaustion and postcastration tests, group-reared MPOA-animals performed at a lower level than control animals. The results are compatible with the hypothesis that play experiences have a role in sparing of copulatory behavior in rats with MPOA-lesions. Deficits in the MPOA-animals in the more challenging tests were discussed in relation to a possible decrease in responsiveness to gonadal or hypothalamic hormones.     

Characteristics of sleep following sexual activity and wheel running in male rats

The EEG sleep patterns of 12 male rats were studied for 4 hr following each of three different conditions: sexual activity, wheel running and no manipulation. Sexual activity was followed by substantial increases in sleep as indicated by several measures. Wheel running produced some enhancement of sleep, but significantly less than did sexual activity. Sleep following sexual activity generally was characterized by fewer, relatively long episodes, whereas that following wheel running was characterized by more short episodes.     

Central tegmental field and sexual behavior in the male rat: effects of neurotoxic lesions

The medial preoptic area/anterior hypothalamus (MPOA/AH) is a key structure in the control of male sexual behavior. This area has reciprocal connections with mesencephalic and brainstem structures including the central tegmental field (CTF). It has been suggested that the CTF receives somatosensory information generated in the genitals promoting activation of the MPOA/AH. In the present study we evaluated the effects of bilateral neurotoxic lesions of the CTF upon male rat sexual behavior. We also explored the effects of these lesions on sociosexual behaviors, partner preference, sexual incentive motivation and motor execution. Tests were performed before and after bilateral quinolinic acid infusions. The lesion was evaluated by quantifying neuronal nuclei (Neu-N) and by the presence of glial fibrillary acidic protein (GFAP) immunohistochemistries. A significant reduction in the percentage of animals displaying mounts, intromissions, and ejaculations was observed in the bilateral and misplaced lesion groups 1 week after the lesion. In the second week post-lesion, only animals with bilateral damage of the CTF showed a significant reduction in sexual behavior. In the third post-lesion test, the percentage of animals displaying sexual behavior returned to control levels. The frequency of pursuit and self-grooming was reduced, and genital exploration was increased after the lesion. Partner preference and sexual incentive motivation were not affected by the lesion suggesting that the CTF is not involved in the appetitive aspects of sexual behavior. Mount, intromission, and ejaculation latency were increased in animals with damage of the CTF and in animals with lesions outside this region. Motor execution was also affected in both groups, suggesting that alterations in latencies could be associated with damage not specific to the CTF.     

Effects of testosterone propionate implants in the brain on the sexual behavior and peripheral tissue of the male rat

The effects of testosterone propionate (TP) implanted in medial preoptic-anterior hypothalamic (MPO-AH) area, caudate-putamen, substantia nigra, and reticular formation on the sexual behavior were studied in castrated male rats. Either TP or cholesterol (C) was fused to the inside of 20-gauge cannula and bilaterally implanted in the brain of male rats not exhibiting ejaculatory patterns for 3 successive weeks after castration. Ejaculatory patterns were restored by TP implanted in all of the neural areas studied. No ejaculations were recorded in C-implanted animals. While the MPO-AH implanted animals tended to show ejaculatory patterns more frequently and in more tests than those having implants in other areas, the differences among groups were not statistically significant. Seminal vesicle weights and histological appearance of the seminal vesicles of TP-implanted animals were not reliably different from those implanted with C. Glans penis epithelium, however, was significantly more stimulated in the TP- than in C-implanted animals. Thus, evidence was obtained that androgen from the implants entered the general circulation and reached somatic organs and probably other neural areas. Using the hormone implantation technique, therefore, no reliable evidence was obtained to conclude that the MPO-AH is a special site for selectively utilizing androgen for controlling male sexual behavior.     

Autoradiographic localization of DI-like dopamine receptors in the forebrain of male and female Japanese quail and their relationship with immunoreactive tyrosine hydroxylase

The distribution of Dl-like dopamine receptors was studied in the brain of male and female Japanese quail (Coturniz japonica) by means of quantitative autoradiography with 3H-labelled D1 selective antagonist, SCH 23390, serving as a ligand. A specific, saturable, high affinity binding of this ligand was demonstrated. High densities of binding sites were detected in the lobus parolfactorius, olfactory tubercle, and paleostriatum augmentatum. Medium densities were observed in the entire neostriatum and in the external layers of the optic tectum. Similar levels of binding outlined the paleostriatum primitivum, the nucleus pretectalis and the nucleus intercollicularis. Low but significant levels of receptors were also present in the medial preoptic area at the level of the sexually dimorphic medial preoptic nucleus and throughout the infundibulum, as well as in the ectostriatum, medial and lateral septum, and nucleus accumbens. At the level of the medial septum, just dorsal to the anterior commissure, two circular areas of high receptor density corresponding to the nucleus of the septal commissure were also observed. No sex difference in receptor density could be detected in any of these areas. All areas containing high densities of D1 receptors also contained high densities of tyrosine hydroxylase (TH) fibers. However, certain areas characterized by a high density of TH-immunoreactive fibers did not contain appreciable densities of D1-like dopamine receptors. The distribution of this receptor and its relationship to TH-immunoreactivity is consistent with observations made in other vertebrates, suggesting that the dopaminergic system is evolutionarily highly conserved among amniote vertebrates.     

Brain-spinal cord neural circuits controlling male sexual function and behavior

Men and women exhibit differences in sexual behavior. This indicates that neural circuits within the central nervous system (CNS) that control sexual behavior differ between the sexes, although differences in behavior are also influenced by sociocultural and hormonal factors. Sexual differentiation of the body and brain occurs during the embryonic and neonatal periods in humans and persists into adulthood with relatively low plasticity. Male sexual behavior is complex and depends on intrinsic and extrinsic factors, including olfactory, somatosensory and visceral cues. Many advances in our understanding of sexually dimorphic neural circuits have been achieved in animal models, but major issues are yet to be resolved. This review summarizes the sexually dimorphic nuclei controlling male sexual function in the rodent CNS and focuses on the interactions of the brain-spinal cord neural networks controlling male sexual behavior. Possible factors that relate findings from animal studies to human behavior are also discussed.     

Ultrasonic vocalizations in male deer mice (Peromyscus maniculatus bairdi): Their role in male sexual behavior

The occurrence of 35-kHz ultrasonic vocalizations was examined during sexual behavior tests in deer mice (Peromyscus maniculatus bairdi). Males which copulated always preceded the onset of copulation with ultrasonic calls. In males failing to exhibit copulatory behavior, ultrasonic emissions were seldom detected. Among copulating males, vocalization rate was highest before copulation and after ejaculation, and declined during copulation. Also, precopulatory vocalization rate was inversely related to the length of time from production of first ultrasound to first intromission. It is suggested that 35-kHz vocalizations of male deer mice may be an important component of their sexual behavior repertoire which serves to facilitate mating.     

Midbrain reticular formation lesions: Habituation to stimulation and copulatory behavior in male rats

Male rats with lesions in the midbrain reticular formation did not habituate in a measure of reactivity to handling stimuli as did operated controls and normals. Comparison of preoperative and postoperative copulatory behavior in male rats with midbrain reticular formation lesions, and copulatory behavior in control operates, and normals revealed that the midbrain lesions left copulatory behavior essentially intact except for some increase in the latency to the first mount.     

Telencephalic and preoptic areas integrate sexual behavior in hime salmon (landlocked red salmon, Oncorhynchus nerka): results of electrical brain stimulation experiments

Various patterns of sexual behavior were evoked in freely swimming hime salmon by electrical stimulation of specific loci in the telencephalon and the preoptic area (POA) using chronically implanted electrodes. Furthermore, co-ordinated sexual behavior corresponding to stages of the natural spawning sequence was elicited from some of these brain regions. These results suggest that (1) sexual behavior is integrated in specific parts of the telencephalon and POA, and (2) within these regions there is a hierarchy of neural systems which mediate progressively more complete components of normal sexual behavior.     

Does sexual coercion play a role in the high-risk sexual behavior of adolescent and young adult women?

Sexual coercion and its relationship to high-risk sexual behavior were examined in five samples of young women. Sample 1 (N=22) consisted of sexually active adolescents aged 15 to 19. Samples 2 (N=206) and 3 (N=70) were recruited from among patients at three sexually transmitted disease clinics. Sample 4 (N=51) consisted of young homeless women living on the street in a large city. Sample 5 (N=51) was recruited from among young women on a college campus. Across all samples, 44.4% of women indicated that they had been forced into some form of sexual activity against their will. Self-reports of sexually coercive experiences were consistently related to risky sexual behavior. It appears that many young women are coerced into engaging in high-risk sexual behavior. This implies the need for greater attention to male coercive sexual behavior and women's skills for coping with such behavior.Support for this paper was provided by Grant HD 26249 from the National Institute of Child Health and Human Development and Grant MH45651 from the National Institute of Mental Health.     

Facilitation of male rat copulatory behavior by electrical stimulation of the medial preoptic area

Lesion studies have demonstrated that the medial preoptic area (MPO) plays a critical role in male rat copulatory behavior. The present study attempted to better localize the neural elements mediating this behavior pattern and to determine the influence of preoptic area stimulation on particular aspects of copulatory behavior. Monopolar stimulating electrodes were implanted in the medial preoptic-anterior hypothalamic continuum or the lateral preoptic-medial forebrain bundle region. The effects of stimulating a particular locus were measured by comparing each animal's behavior on repeated stimulation and control tests. All measures of copulatory activity taken were facilitated by medial, but not by lateral, preoptic stimulation. The most common change produced by MPO stimulation was a reduction in both the number of mounts and intromissions preceding ejaculation. Short-latency approach and mounting of the female and greatly reduced refractory periods were also seen in two MPO animals. No evidence of a post-stimulation inhibition of copulatory behavior resulting from the stimulation itself was seen in these two animals. Most animals in both the medial and lateral groups learned to self-stimulate (SS) using the same 30-sec trains of stimulation as used in earlier tests of copulatory activity. SS rate, stimulation-bound copulation, and degree of facilitation of ejaculation were positively correlated in MPO, but not in lateral preoptic animals.     

Dopamine and serotonin: influences on male sexual behavior

Steroid hormones regulate sexual behavior primarily by slow, genomically mediated effects. These effects are realized, in part, by enhancing the processing of relevant sensory stimuli, altering the synthesis, release, and/or receptors for neurotransmitters in integrative areas, and increasing the responsiveness of appropriate motor outputs. Dopamine has facilitative effects on sexual motivation, copulatory proficiency, and genital reflexes. Dopamine in the nigrostriatal tract influences motor activity; in the mesolimbic tract it activates numerous motivated behaviors, including copulation; in the medial preoptic area (MPOA) it controls genital reflexes, copulatory patterns, and specifically sexual motivation. Testosterone increases nitric oxide synthase in the MPOA; nitric oxide increases basal and female-stimulated dopamine release, which in turn facilitates copulation and genital reflexes. Serotonin (5-HT) is primarily inhibitory, although stimulation of 5-HT(2C) receptors increases erections and inhibits ejaculation, whereas stimulation of 5-HT(1A) receptors has the opposite effects: facilitation of ejaculation and, in some circumstances, inhibition of erection. 5-HT is released in the anterior lateral hypothalamus at the time of ejaculation. Microinjections of selective serotonin reuptake inhibitors there delay the onset of copulation and delay ejaculation after copulation begins. One means for this inhibition is a decrease in dopamine release in the mesolimbic tract.     

Conditioned suppression of sexual behavior in stallions and reversal with diazepam

Sexual behavior dysfunction unaccompanied by detectable physical or endocrine abnormality is an important cause of reproductive failure among domestic stallions. Several authors have suggested that such dysfunction may be psychogenic, related to negative experience associated with intense handling and training. An experimental model of experience-related dysfunction was developed by exposing pony stallions to erection-contingent aversive conditioning. This resulted in rapid, specific suppression of sexual arousal and response similar to spontaneously occurring dysfunction. Subsequently, treatment with a CNS-active benzodiazepine derivative (diazepam) reversed these effects.     

Effects of laryngeal denervation on ultrasound production and male sexual behavior in rodents

Adult male house mice (Mus musculus) and deer mice (Peromyscus maniculatus bairdi) were used to investigate the effects of partial denervation of the larynx on ultrasound production. In addition the masculine sexual behavior of vocalizing and muted males was assessed on tests with receptive females. For both species, unilateral transections of the inferior laryngeal nerve (ILN) significantly reduced the proportion of males that emitted ultrasonic vocalizations. However, the inability to vocalize did not prevent the display of male sexual behavior. Bilateral transections of the superior laryngeal nerve (SLN) failed to abolish ultrasound production in males of both species. These nerve transections, however, reduced the amount of ultrasound recorded during postsurgical tests, and in the case of deer mice, cuts of the SLN increased the latency to the first vocalization. The present results confirm the importance of the ILN in the neural control of ultrasonic vocalizations and indicate that, at least in laboratory tests, the ability to emit ultrasounds is not a necessary condition for the display of mating behavior in male rodents.     

Food conditioning, castration, testosterone administration and sexual behavior in the male rat

Chronically food-deprived male rats, when paired with a female rat in heat, were rewarded by receiving a food pellet following each intromission. Following castration there was a rapid decline in all aspects of male sexual behavior: after 3 weeks all sex behavior had stopped. There were no differences between the conditioned males and their yoked controls. Substitution with two doses of testosterone (through silastic implants) restored sexual behavior, but equally so in the conditioned and the control animals. Removal of the testosterone implant again caused a very rapid decline in sexual behavior, no differences between experimental and yoked control males. These results suggest that food, as a non-sexual stimulus, does not cause hungry male rats to continue to copulate for prolonged periods following castration. Furthermore, the combination of chronic food deprivation plus castration do summate with each other in the very rapid decline and cessation of male sexual performance.     

Nuclear estrogen receptor binding in microdissected brain regions of female rats during pregnancy: Implications for maternal and sexual behavior

Previously, we showed that changes in nuclear estrogen receptor (NER) concentrations within large dissections of the preoptic area and hypothalamus of pregnant rats might underlie changes in both maternal and sexual behaviors. To more precisely localize these biochemical changes, NER concentrations were measured in microdissected nuclei within the preoptic area and hypothalamus of pregnant rats on days 8, 16 and 22. Results indicated that NER levels changed significantly throughout pregnancy and that the magnitude and direction of change was site specific. Although a different pattern of change was found in each nucleus, NER levels in most preoptic area nuclei were significantly higher by the 16th day of pregnancy compared to those on day 8, while receptor levels in most hypothalamic nuclei did not increase until day 22 of pregnancy. The higher NER levels found in preoptic area nuclei of female rats as pregnancy advances can be correlated with growing maternal responsiveness during pregnancy, while elevated concentrations of NER in hypothalamic nuclei at the end of pregnancy may indicate preparation for postpartum estrus.     

Interaction of hypothalamic structures in the mediation of male sexual behavior

A series of studies was conducted in which the influences of medial forebrain bundle (MFB) and medial preoptic area (MPOA) lesions on the copulatory behavior of the male rat were investigated. Previous findings that bilateral electropytic lesions in parafornical MFB or the MPOA abolish sexual behavior were confirmed. Further, it was found that MFB lesions as far anterior as the MPOA, but not rostral to this area, were also effective in abolishing male sexual behavior. Asymmetrical hypothalamic lesions were also employed in an attempt to ascertain the degree of interaction between the MPOA and the MFB in the mediation of male sexual behavior. Unilateral lesions in the MFB combined with contralateral destruction of the MPOA were also found to effectively suppress mating. These findings were interpreted as supporting suggestions that portions of the MFB function as a caudally directed pathway from the MPOA in the mediation of sexual behavior. Attempts to reverse the effects on sexual behavior of MFB lesions by the administration of dl-5-hydroxytryptophan were not successful. On the contrary, this chemical was found to be inhibitory to male sexual behavior.     

The interaction of photoperiod and testosterone on the development of copulatory behavior in castrated male hamsters

Castrated adult male golden hamsters were maintained on either a stimulatory (LD 14:10) or a nonstimulatory (LD 6:18) light cycle for 10 weeks, and then were implanted subcutaneously with empty or testosterone-filled Silastic capsules of various lengths. Animals were tested for copulatory behavior prior to capsule implantation and 10, 20 and 40 days after implantation. Androgen-treated LD 14:10 hamsters showed a higher incidence of ejaculation on the final trial than did similarly treated LD 6:18 animals. When serum androgen levels were maintained at physiological levels (about 3 ng/ml, from a 20 mm capsule), significantly greater numbers of LD 14:10 hamsters intromitted and ejaculated compared to LD 6:18 animals. Examination of the development of copulation over trials revealed an interaction of photoperiod and androgen: LD 14:10 animals showed significant improvement over trials if stimulated with 8,20 or 100 mm long testosterone capsules, while LD 6:18 animals showed increased copulation over trials only if they were implanted with 100 mm capsules. These results indicate that exposure to short days for 10 weeks renders copulatory behavior of the castrate male hamster less responsive to the stimulatory effects of testosterone. This alteration in sensitivity to androgen may be one way in which the photoperiod acts to decrease copulation in seasonally breeding animals.