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The Journal of Neuroscience, March 14, 2007, 27(11):2837-2845; doi:10.1523/JNEUROSCI.4121-06.2007

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Behavioral/Systems/Cognitive
A Role for Hypocretin (Orexin) in Male Sexual Behavior

John W. Muschamp,^1,4 Juan M. Dominguez,^1,5 Satoru M. Sato,^2,4 Roh-Yu Shen,³ and Elaine M. Hull^1,4

¹Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, Florida 32306, ²Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, ³Research Institute on Addictions, University at Buffalo, State University of New York, Buffalo, New York 14203, ⁴Department of Psychology, University at Buffalo, State University of New York, Buffalo, New York 14260, and ⁵Department of Psychology, American University, Washington, DC 20016

Correspondence should be addressed to John Muschamp, Department of Psychology, Florida State University, Tallahassee, FL 32306-1270. Email: muschamp{at}neuro.fsu.edu

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) receptors revealed no colocalization of hcrt/orx with AR and few hcrt/orx neurons expressing ER, 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.

Key words: hypocretin/orexin; dopamine; ventral tegmental area; sexual behavior; male rats; electrophysiology

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Received April 21, 2006; revised Jan. 23, 2007; accepted Feb. 8, 2007.

Correspondence should be addressed to John Muschamp, Department of Psychology, Florida State University, Tallahassee, FL 32306-1270. Email: muschamp{at}neuro.fsu.edu

This article has been cited by other articles:

				S. L. Borgland, S.-J. Chang, M. S. Bowers, J. L. Thompson, N. Vittoz, S. B. Floresco, J. Chou, B. T. Chen, and A. Bonci Orexin A/Hypocretin-1 Selectively Promotes Motivation for Positive Reinforcers J. Neurosci., September 9, 2009; 29(36): 11215 - 11225. [Abstract] [Full Text] [PDF]

				M. Ramanjaneya, A. C Conner, J. Chen, P. Kumar, J. E P Brown, O. Johren, H. Lehnert, P. R Stanfield, and H. S Randeva Orexin-stimulated MAP kinase cascades are activated through multiple G-protein signalling pathways in human H295R adrenocortical cells: diverse roles for orexins A and B J. Endocrinol., August 1, 2009; 202(2): 249 - 261. [Abstract] [Full Text] [PDF]

				A. Adamantidis and L. de Lecea The hypocretins as sensors for metabolism and arousal J. Physiol., January 1, 2009; 587(1): 33 - 40. [Abstract] [Full Text] [PDF]

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