The overall long-term objective of this research proposal is to characterize neurochemical influences on male sexual motivation and behavior of primates. Although much is known regarding neurochemical control of rodent sexual behavior, very little progress has been made with regards to our understanding of these mechanisms in primate species. Recent studies in our laboratory indicate that male sexual behavior of rhesus monkeys is affected by treatment with agents that alter dopamine (DA) and serotonin (5-HT) activity. Based on these findings, experiments outlined in this proposal will investigate the role of DA and 5-HT in regulating male sexual behavior of rhesus monkeys. Two hypothesis will be evaluated: 1) Pharmacologic manipulations that increase DA stimulation, particularly at D2 receptor sites, facilitate male sexual behavior; whereas manipulations that decrease DA activity, particularly at D2 receptor sites, result in deficits in male sexual behavior. 2) Pharmacological manipulations that decrease 5-HT activity, either by stimulating 5-HT1A autoreceptors or blocking 5-HT2 receptors, facilitate male ejaculation; whereas manipulations that increase 5-HT activity, either by blocking 5- HT1A autoreceptors or stimulating 5-HT2 receptors, impair male ejaculatory performance. Two novel sexual behavior testing paradigms will be utilized in these projects. The first will assess noncopulatory aspects of male sexual behavior by observing the monkey's performance of penile erections, courtship behavior and masturbatory behavior in response to sexual stimuli that they can see, hear and smell, but not physically contact. The second testing paradigm will be used to evaluate male copulatory performance and ejaculatory potency by observing the monkey's mating performance when paired daily with a sexually receptive female for six hours. With the incidence of sexual dysfunction (i.e. impotence and loss of libido) among normal men being approximately 7-10%, and an even higher incidence rate among elderly men and clinically ill patients, there is clearly a need to develop a better understanding of organic factors regulating sexual behavior. In this regard, elucidation of the neurochemical mechanisms involved in the regulation of primate sexual behavior may minimize the potential of clinicians utilizing psychotropic agents that have adverse effects on sexual behavior and may foster the development of effective treatments for human male sexual dysfunction.
