title: A role for hypocretin (orexin) in male sexual behavior.
abstract: The role of hypocretin (orexin; hcrt/orx) neurons in regulation of arousal is well established. Recently, hcrt/orx has been implicated in food reward and drug-seeking behavior. We report here that in male rats, Fos immunoreactivity (ir) in hcrt/orx neurons increases markedly during copulation, whereas castration produces decreases in hcrt/orx neuron cell counts and protein levels in a time course consistent with postcastration impairments in copulatory behavior. This effect was reversed by estradiol replacement. Immunolabeling for androgen (AR) and estrogen (ER alpha) receptors revealed no colocalization of hcrt/orx with AR and few hcrt/orx neurons expressing ER alpha, suggesting that hormonal regulation of hcrt/orx expression is via afferents from neurons containing those receptors. We also demonstrate that systemic administration of the orexin-1 receptor antagonist SB 334867 [N-(2-methyl-6-benzoxazolyl)-N''-1,5-naphthyridin-4-yl urea] impairs copulatory behavior. One locus for the prosexual effects of hcrt/orx may be the ventral tegmental area (VTA). We show here that hcrt-1/orx-A produces dose-dependent increases in firing rate and population activity of VTA dopamine (DA) neurons in vivo. Activation of hcrt/orx during copulation, and in turn, excitation of VTA DA neurons by hcrt/orx, may contribute to the robust increases in nucleus accumbens DA previously observed during male sexual behavior. Subsequent triple immunolabeling in anterior VTA showed that Fos-ir in tyrosine hydroxylase-positive neurons apposed to hcrt/orx fibers increases during copulation. Together, these data support the view that hcrt/orx peptides may act in a steroid-sensitive manner to facilitate the energized pursuit of natural rewards like sex via activation of the mesolimbic DA system.
authors.affiliation: Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, Florida 32306, USA. muschamp@neuro.fsu.edu
authors.forename: John W
authors.initials: JW
authors.lastname: Muschamp
authors.forename: Juan M
authors.initials: JM
authors.lastname: Dominguez
authors.forename: Satoru M
authors.initials: SM
authors.lastname: Sato
authors.forename: Roh-Yu
authors.initials: RY
authors.lastname: Shen
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Hull
mesh_terms: D000818:Animals; D005260:Female; D012739:Gonadal Steroid Hormones / Q000032:analysis / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000502:physiology; D009479:Neuropeptides / Q000032:analysis / Q000502:physiology*; D009919:Orchiectomy; D000068797:Orexins; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D012726:Sexual Behavior, Animal / Q000502:physiology*; D017557:Ventral Tegmental Area / Q000737:chemistry / Q000502:physiology
chemical_list: D012739:Gonadal Steroid Hormones; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins