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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
7R01DA014591-05
Application #
7060953
Study Section
Special Emphasis Panel (ZRG1-IFCN-4 (05))
Program Officer
Volman, Susan
Project Start
2002-05-10
Project End
2007-04-30
Budget Start
2006-01-01
Budget End
2006-04-30
Support Year
5
Fiscal Year
2005
Total Cost
$185,066
Indirect Cost
Name
University of Western Ontario
Department
Type
DUNS #
208469452
City
London
State
ON
Country
Canada
Zip Code
N6 3-K7
Di Sebastiano, Andrea R; Wilson-Perez, Hilary E; Lehman, Michael N et al. (2011) Lesions of orexin neurons block conditioned place preference for sexual behavior in male rats. Horm Behav 59:1-8
Davis, Jon F; Loos, Maarten; Di Sebastiano, Andrea R et al. (2010) Lesions of the medial prefrontal cortex cause maladaptive sexual behavior in male rats. Biol Psychiatry 67:1199-204
Frohmader, Karla S; Pitchers, Kyle K; Balfour, Margaret E et al. (2010) Mixing pleasures: review of the effects of drugs on sex behavior in humans and animal models. Horm Behav 58:149-62
Frohmader, Karla S; Bateman, Katherine L; Lehman, Michael N et al. (2010) Effects of methamphetamine on sexual performance and compulsive sex behavior in male rats. Psychopharmacology (Berl) 212:93-104
Frohmader, K S; Wiskerke, J; Wise, R A et al. (2010) Methamphetamine acts on subpopulations of neurons regulating sexual behavior in male rats. Neuroscience 166:771-84
Pitchers, Kyle K; Balfour, Margaret E; Lehman, Michael N et al. (2010) Neuroplasticity in the mesolimbic system induced by natural reward and subsequent reward abstinence. Biol Psychiatry 67:872-9
Di Sebastiano, Andrea R; Yong-Yow, Sabrina; Wagner, Lauren et al. (2010) Orexin mediates initiation of sexual behavior in sexually naive male rats, but is not critical for sexual performance. Horm Behav 58:397-404
Tenk, Christine M; Wilson, Hilary; Zhang, Qi et al. (2009) Sexual reward in male rats: effects of sexual experience on conditioned place preferences associated with ejaculation and intromissions. Horm Behav 55:93-7
Straiko, Megan M W; Gudelsky, Gary A; Coolen, Lique M (2007) Treatment with a serotonin-depleting regimen of MDMA prevents conditioned place preference to sex in male rats. Behav Neurosci 121:586-93
Dominguez, Juan M; Balfour, Margaret E; Lee, Han S et al. (2007) Mating activates NMDA receptors in the medial preoptic area of male rats. Behav Neurosci 121:1023-31

Showing the most recent 10 out of 14 publications