A Role for Hypocretin (Orexin) in Male Sexual Behavior
Open Access
- 14 March 2007
- journal article
- research article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 27 (11), 2837-2845
- https://doi.org/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 (ERα) receptors revealed no colocalization of hcrt/orx with AR and few hcrt/orx neurons expressing ERα, 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) neuronsin 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.This publication has 63 references indexed in Scilit:
- Arousal and reward: a dichotomy in orexin functionTrends in Neurosciences, 2006
- Innervation of orexin/hypocretin neurons by GABAergic, glutamatergic or cholinergic basal forebrain terminals evidenced by immunostaining for presynaptic vesicular transporter and postsynaptic scaffolding proteinsJournal of Comparative Neurology, 2006
- Direct Involvement of Orexinergic Systems in the Activation of the Mesolimbic Dopamine Pathway and Related Behaviors Induced by MorphineJournal of Neuroscience, 2006
- Comparison of melanin-concentrating hormone and hypocretin/orexin mRNA expression patterns in a new parceling scheme of the lateral hypothalamic zoneNeuroscience Letters, 2005
- Neuronal nitric oxide synthase and gonadal steroid interaction in the MPOA of male rats: Co-localization and testosterone-induced restoration of copulation and nNOS-immunoreactivityBrain Research, 2005
- The hypocretins: Setting the arousal thresholdNature Reviews Neuroscience, 2002
- Modulation of Brain Reward Circuitry by LeptinScience, 2000
- Dopamine-cell depolarization block as a model for the therapeutic actions of antipsychotic drugsTrends in Neurosciences, 1997
- Toward a cellular analysis of intracranial self-stimulation: Contributions of collision studiesNeuroscience & Biobehavioral Reviews, 1989
- Food reward and cocaine increase extracellular dopamine in the nucleus accumbens as measured by microdialysisLife Sciences, 1988