Role of Endogenous Opioids in Male Reproductive Behavior

内源性阿片类药物在男性生殖行为中的作用

• 批准号: 6620724
• 负责人: Lique M Coolen
• 金额: $ 26.78万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-10 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6620724
• 关键词: antisense nucleic acid; behavior test; behavioral /social science research tag; biomarker; confocal scanning microscopy; electron microscopy; endogenous opioid; endorphins; enkephalins; fos protein; immunocytochemistry; laboratory rat; male; neural transmission; neuroanatomy; neuropharmacology; neuroregulation; opioid receptor; preoptic areas; protein localization; psychopharmacology; receptor expression; sex behavior

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.

这项研究的目的是通过 哪种内源性阿片类肽坐标男性生殖行为。这 阿片类药物和阿片类肽对男性交配行为的影响 已经讨论了几个世纪。综上所述，这些研究导致了 假设内源性阿片类肽在性行为期间被释放。 但是，迄今为止，内源性肽的释放和作用的位点 仍然不清楚。另外，未知行为的哪个方面 导致肽的释放以及这些肽的精确身份 阿片类肽。此外，阿片类药物作用的行为意义 不清楚。因此，当前的建议将解决这些问题。 首先，我们将建立a）在性行为期间，b）在哪个站点 阿片类药物在交配过程中起作用。提出的实验将调查 MU阿片受体的内在化，以了解特定地点 伴随动机和完善的反应的变化 性行为。令人兴奋的是，我们实验室的初步数据已经 表现出雄性大鼠前大鼠的MU阿片受体的内在化 交配后下丘脑的面积。此外，哪个问题 在性行为期间释放内源性阿片类肽将是 使用标记来解决神经激活和电子显微镜 可视化阿片类肽末端和MU阿片类药物之间的突触接触 受体神经元。最后，阿片类药物激活的行为意义 性行为引起的受体将使用药理测试 对受体的操纵以及减少翻译的反义应用 受体RNA。 这些研究将为细胞水平提供第一个证据 男性性行为期间阿片类肽作用的定位。这会 当前可用的阿片类药物对性的药理作用 行为，通过提供有关这些效果的解剖学特异性的数据。 此外，拟议的研究将提高我们对 内源性阿片类肽参与自然发生的动机 行为。由于自然动机行为的潜在途径具有 与涉及药物滥用的电路的重叠，研究 因此，内源性阿片类药物在自然动机中的作用也可能揭示 有关滥用药物的潜在机制的重要信息。