Elaine M. Hull

Pharmacological analysis of male rat sexual behavior

Pharmacological influences on male rat sexual behavior are reviewed in an attempt to identify neurotransmitters and their respective receptor types that regulate various factors comprising the behavioral pattern. Evidence is presented that: (1) serotonergic influence is generally inhibitory to sexual behavior, although two receptor subtypes may lower ejaculation threshold; (2) dopaminergic agonists facilitate several aspects of copulatory behavior and ex copula genital responses; (3) noradrenergic activity appears to increase sexual arousal; (4) cholinergic agonists facilitate ejaculation, or in some cases, delay or prevent initiation of copulation; (5) GABA agonists inhibit sexual responses both in and ex copula; (6) opiate agonists appear to inhibit copulation and penile reflexes, although antagonists have mixed effects; (7) ACTH and MSH peptides promote copulatory behavior and genital responses; (8) oxytocin facilitates ex copula penile responses, but may contribute to postejaculatory refractoriness; and (9) long-term exposure to prolactin inhibits sexual behavior and penile responses. Although some progress has been made in identifying neurotransmitter-receptor effects on behavioral components, copulatory behavior is complex and no drug has been found to affect only a single component. Furthermore, drug specificity is only relative.

Male Sexual Behavior

Major areas controlling sexual motivation and performance in males include the mesolimbic dopamine (DA) system, the medial preoptic area (MPOA), the amygdala, and the bed nucleus of the stria terminalis (BST). Genital reflexes are controlled by the MPOA, paraventricular nucleus (PVN), brainstem, and spinal cord areas. Mating is integrated by the MPOA, amygdala, BST, PVN, and mesolimbic and nigrostriatal tracts, which are also important for other social behaviors. Perinatal and adult hormones predispose the network to produce specific behaviors. Steroid hormones have primarily slow, genomically mediated effects, although they may also have rapid effects mediated by membrane receptors.

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.

Hormone-neurotransmitter interactions in the control of sexual behavior

The stimuli from a receptive female and/or copulation itself leads to the release of dopamine (DA) in at least three integrative hubs. The nigrostriatal system promotes somatomotor activity; the mesolimbic system subserves numerous types of motivation; and the medial preoptic area (MPOA) focuses the motivation onto specifically sexual targets, increases copulatory rate and efficiency, and coordinates genital reflexes. The previous (but not necessarily concurrent) presence of testosterone is permissive for DA release in the MPOA, both during basal conditions and in response to a female. One means by which testosterone may increase DA release is by upregulating nitric oxide synthase, which produces nitric oxide, which in turn increases DA release. Hormonal priming in females may also increase DA release in the MPOA, and copulatory activity may further increase DA levels in females. One of the intracellular effects of stimulation of DA D1 receptors in the MPOA of male rats may be increased expression of the immediate-early gene c-fos, which may mediate longer term responses to copulation. Furthermore, increased sexual experience led to increased immunoreactivity to Fos, the protein product of c-fos, following copulation to one ejaculation. Another intracellular mediator of DAs effects, particularly in castrates, may be the phosphorylation of steroid receptors. Finally, while DA is facilitative to copulation, 5-HT is generally inhibitory. 5-HT is released in the LHA, but not in the MPOA, at the time of ejaculation. Increasing 5-HT in the LHA by microinjection of a selective serotonin reuptake inhibitor (SSRI) increased the latency to begin copulating and also the latency to the first ejaculation, measured from the time the male first intromitted. These data may at least partially explain the decrease in libido and the anorgasmia of people taking SSRI antidepressants. One means by which LHA 5-HT decreases sexual motivation (i.e. increases the latency to begin copulating) may be by decreasing DA release in the NAcc, a major terminal of the mesolimbic system. Thus, reciprocal changes in DA and 5-HT release in different areas of the brain may promote copulation and sexual satiety, respectively.

Psychophysical studies of monkey vision—I. Macaque luminosity and color vision tests

Abstract Macaque monkeys and normal human observers were tested on the same apparatus for the presence of a Purkinje shift, and for spectral sensitivity under scotopic and photopic conditions. The flicker fusion point for different lights was used as a measure of visual sensitivity in these tests and the testing procedure was a four-alternative forced choice. The results show that macaque monkeys and normal human observers show a rod-cone break at the same flicker frequency, and are very similar in both relative and absolute scotopic and photopic sensitivity. Macaque monkeys, normal human observers and color-defective human observers were also tested under identical conditions in several measures of color vision.

Dopamine, the medial preoptic area, and male sexual behavior

The medial preoptic area (MPOA), at 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.

Dopaminergic control of male sex behavior in rats: Effects of an intracerebrally-infused agonist

Systemically-administered dopaminergic drugs have been found to facilitate sexual behavior of men and male rats. The present experiments investigated the localization within the brain of dopaminergic effects on copulation of male rats. Apomorphine, a dopamine agonist, was microinfused into the medial preoptic area, caudate-putamen, nucleus accumbens, lateral septum and lateral ventricle. The lowest dose of apomorphine (0.2 microgram) infused into the ventricle reduced the number of ejaculations, slowed the rate of intromitting and decreased the percentage of mounts on which the male gained vaginal intromission. The higher two doses (0.5 and 2.0 micrograms) infused into the medial preoptic area and, in some cases, the ventricle, increased the number of ejaculations and the percentage of mounts with vaginal intromission, increased the rate of intromitting and decreased the latency to ejaculate and the postejaculatory interval before resuming copulation. Infusions into the caudate-putamen and lateral septum were without effect. Those into nucleus accumbens produced only a slight dose-related decrease in latency to begin copulating. The copulatory impairments associated with infusions of the lowest dose into the ventricle may have resulted from stimulation of autoreceptors, or from preferential stimulation by low doses of an undetermined area. The facilitative effects of the two higher doses into the medial preoptic area and lateral ventricle may have been due to stimulation of dopaminergic postsynaptic receptors.

Nitric oxide increases dopamine and serotonin release in the medial preoptic area

NITRIC oxide (NO) is becoming recognized as an important intercellular messenger in the brain. The present experiment used microdialysis to examine the potential role of NO in the regulation of dopamine (DA) and serotonin (5-HT) release in the medial preoptic area (MPOA) of freely moving male rats. The NO precursor L-arginine (L-Arg, 100 μM), administered into the MPOA via the dialysis probe, increased extracellular levels of DA, 5-HT, and the major metabolites of DA. These increases were blocked by the coadministration of the NO synthase inhibitor N-monomethyl L-arginine (NMMA, 400 μM). The inactive isomer D-arginine (100 μM) was ineffective, and NMMA by itself decreased DA below baseline levels. Thus, NO may modulate the release of DA and 5-HT in the MPOA.

Women's Orgasm

Abstract An orgasm in the human female is a variable, transient peak sensation of intense pleasure, creating an altered state of consciousness, usually with an initiation accompanied by involuntary, rhythmic contractions of the pelvic striated circumvaginal musculature, often with concomitant uterine and anal contractions, and myotonia that resolves the sexually induced vasocongestion and myotonia, generally with an induction of well-being and contentment. Womens orgasms can be induced by erotic stimulation of a variety of genital and nongenital sites. As of yet, no definitive explanations for what triggers orgasm have emerged. Studies of brain imaging indicate increased activation at orgasm, compared to pre-orgasm, in the paraventricular nucleus of the hypothalamus, periaqueductal gray of the midbrain, hippocampus, and the cerebellum. Psychosocial factors commonly discussed in relation to female orgasmic ability include age, education, social class, religion, personality, and relationship issues. Findings from surveys and clinical reports suggest that orgasm problems are the second most frequently reported sexual problems in women. Cognitive-behavioral therapy for anorgasmia focuses on promoting changes in attitudes and sexually relevant thoughts, decreasing anxiety, and increasing orgasmic ability and satisfaction. To date there are no pharmacological agents proven to be beneficial beyond placebo in enhancing orgasmic function in women.

Testosterone, preoptic dopamine, and copulation in male rats.

Steroid hormones prime neural circuits for sexual behavior, in part by regulating enzymes, receptors, or other proteins affecting neurotransmitter function. Dopamine facilitates male sexual behavior in numerous species and is released before and/or during copulation in three integrative neural systems. The nigrostriatal system enhances readiness to respond; the mesolimbic system promotes many appetitive behaviors; the medial preoptic area (MPOA) contributes to sexual motivation, genital reflexes, and copulation. We have reported a consistent relationship between precopulatory dopamine release in the MPOA, when an estrous female was behind a perforated barrier, and the ability to copulate after the barrier was removed. Recent, but not concurrent, testosterone was necessary for the precopulatory dopamine response and copulation. The deficit in MPOA dopamine release in castrates was observed in basal conditions as well as the sexual context. However, dopamine in tissue punches from castrates was higher than in intact males. Because tissue levels represent primarily stored neurotransmitter, dopamine appeared to have been synthesized normally, but was not being released. Amphetamine induced greater dopamine release in castrates, again suggesting excessive dopamine storage. The decreased release may result from decreased activity of nitric oxide synthase in the MPOA of castrates. A marker for this enzyme showed lower activity in castrates than in intact males. Finally, blocking nitric oxide synthase in intact males blocked the copulation-induced release of dopamine in the MPOA. Therefore, one means by which testosterone may promote copulation is by upregulating nitric oxide synthesis in the MPOA, which in turn enhances dopamine release.