The goal of this research is to elucidate neural mechanisms by which endogenous opioid peptides coordinate male reproductive behavior. The effects of opiates and opioid peptides on masculine copulatory behavior have been discussed for centuries. Taken together, these studies lead to the hypothesis that endogenous opioid peptides are released during sexual behavior. However, to date, the site(s) of release and action of the endogenous peptides are still unclear. In addition it is unknown which aspect of the behavior causes the release of the peptides, as well as the precise identity of these opioid peptides. Moreover, the behavioral significance of the action of opioids is unclear. Therefore, the current proposal will address these questions. First we will establish a) when during sexual behavior, and b) at which sites opioids are acting during mating. The proposed experiments will investigate internalization of mu opioid receptors in order to understand site-specific changes accompanying the motivational and consummatory responses underlying sexual behavior. Excitingly, preliminary data from our laboratory has already demonstrated internalization of the mu opioid receptor in the male rat preoptic area of the hypothalamus following copulation. Furthermore, the question which endogenous opioid peptides are released during sexual behavior will be addressed using markers for neural activation and electron microscopy to visualize synaptic contacts between opioid peptide terminals and mu opioid receptor neurons. Finally, the behavioral significant of activation of opioid receptors induced by sexual behavior, will be tested using pharmacological manipulations of the receptor, and antisense application to reduce translation of receptor RNA. These studies will provide the first evidence, at a cellular level, for the localization of opioid peptide action during male sexual behavior. This will augment currently available pharmacological effects of opioids on sexual behavior, by providing data on the anatomical specificity of these effects. Moreover, the proposed research will advance our understanding of the involvement of endogenous opioid peptides in a naturally occurring motivated behavior. Since the pathways underlying natural motivated behaviors have striking overlaps with the circuitries involved in substance abuse, studying the role of endogenous opioids for natural motivation may therefore also reveal important information regarding the underlying mechanisms of substance abuse.
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