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Hypocretin (Orexin), Dopamine, and Goal-Directed Behavior

Title: Hypocretin (Orexin), Dopamine, and Goal-Directed Behavior.
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Name(s): Muschamp, John W. (John Whitney), 1974-, author
Hull, Elaine, professor directing dissertation
Quadagno, David, outside committee member
Joiner, Thomas, committee member
Kabbaj, Mohamed, committee member
Wang, Zuoxin, committee member
Department of Psychology, degree granting department
Florida State University, degree granting institution
Type of Resource: text
Genre: Text
Issuance: monographic
Date Issued: 2007
Publisher: Florida State University
Place of Publication: Tallahassee, Florida
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: 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. I report here that in male rats, Fos-immunoreactivity (ir) in hcrt/orx neurons increases markedly during copulation and with estrous female cues, while castration produces decreases in hcrt/orx neuron cell counts and protein levels in a time course consistent with post-castration 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. Double-immunolabeling for ERα and melanin concentrating hormone (MCH) showed no expression of this receptor in MCH cells adjacent to hcrt/orx neurons. I also demonstrate that systemic administration of the orexin-1 receptor (OX1) antagonist SB 334867 impairs copulatory behavior. One locus for hcrt/orx's pro-sexual effects may be the ventral tegmental area (VTA). I show 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.
Identifier: FSU_migr_etd-2164 (IID)
Submitted Note: A Dissertation Submitted to the Department of Psychology in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy.
Degree Awarded: Spring Semester, 2007.
Date of Defense: March 27, 2007.
Keywords: Hypocretin (Orexin), Reproductive Behavior, Neuroendocrinology, Motivated Behavior, Peptides, Dopamine, Ventral Tegmental Area
Bibliography Note: Includes bibliographical references.
Advisory Committee: Elaine Hull, Professor Directing Dissertation; David Quadagno, Outside Committee Member; Thomas Joiner, Committee Member; Mohamed Kabbaj, Committee Member; Zuoxin Wang, Committee Member.
Subject(s): Psychology
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_migr_etd-2164
Owner Institution: FSU

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Muschamp, J. W. (J. W. ). (2007). Hypocretin (Orexin), Dopamine, and Goal-Directed Behavior. Retrieved from http://purl.flvc.org/fsu/fd/FSU_migr_etd-2164