A role for hypocretin (orexin) in male sexual behavior

J Neurosci. 2007 Mar 14;27(11):2837-45. doi: 10.1523/JNEUROSCI.4121-06.2007.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Female
  • Gonadal Steroid Hormones / analysis
  • Gonadal Steroid Hormones / physiology
  • Intracellular Signaling Peptides and Proteins / analysis
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Male
  • Neurons / chemistry
  • Neurons / physiology
  • Neuropeptides / analysis
  • Neuropeptides / physiology*
  • Orchiectomy
  • Orexins
  • Rats
  • Rats, Long-Evans
  • Rats, Sprague-Dawley
  • Sexual Behavior, Animal / physiology*
  • Ventral Tegmental Area / chemistry
  • Ventral Tegmental Area / physiology

Substances

  • Gonadal Steroid Hormones
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins