Orexin A (hypocretin-1) application at the medial preoptic area potentiates male sexual behavior in rats

Gulia, Kamalesh K.; Mallick, Hruda Nanda; Kumar, Velayudhan Mohan

doi:10.1016/s0306-4522(02)00877-1

Cited by 80 publications

(38 citation statements)

References 23 publications

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“…These data are consistent with earlier 2-deoxyglucose studies reporting increased metabolic activity in LHA after exposure to estrous female odors (Orsini et al, 1985). This effect may reflect enhanced hcrt/orx transmission in hcrt/orx neuron terminal areas like the mPOA, in which hcrt/orx has been shown to facilitate male copulatory behavior (Gulia et al, 2003). Sex-related Fos induction in hcrt/orx neurons is consistent with the notion that the hcrt/orx neurons are sensitive to natural reinforcers.…”

Section: Discussionsupporting

confidence: 91%

“…Just as exogenous hcrt/orx can enhance feeding and food seeking (Kotz, 2006), intrahypothalamic infusion of hcrt/orx facilitates male rat sexual behavior (Gulia et al, 2003). In light of classic studies in which feeding or male copulatory behavior was elicited by electrical stimulation of sites in the lateral hypothalamic area (LHA) that are now known to contain hcrt/orx neurons (Vaughan and Fisher, 1962;Caggiula and Hoebel, 1966;Swanson et al, 2005), we sought evidence for the activation of hcrt/orx neurons during copulation and for impairment of the behavior by orexin-1 receptor (OX 1 ) blockade.…”

Section: Introductionmentioning

confidence: 99%

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A Role for Hypocretin (Orexin) in Male Sexual Behavior

Muschamp¹,

Domínguez²,

Sato³

et al. 2007

J. Neurosci.

179

119

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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)-NЉ-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.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

A Role for Hypocretin (Orexin) in Male Sexual Behavior

Muschamp¹,

Domínguez²,

Sato³

et al. 2007

J. Neurosci.

179

119

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“…Additionally, histamine in the ventromedial hypothalamus facilitates both electrical activity and lordosis behavior in female rodents (21,29). Similarly, hypocretin peptides increase overall CNS arousal and microinjections of hypocretin into the medial preoptic area increase male sexual behavior (22). The inverse example also provides evidence for the same point, anesthetics administered before priming doses of estradiol prevent the expression of lordosis behavior and the induction of mating-related genes (30, 31) whereas amphetamine administration facilitates estrogenic induction of mating (32).…”

Section: Discussionmentioning

confidence: 98%

“…As mentioned, a key component of the generalized arousal theory is that alterations in generalized arousal should be able to modulate the strength of specific motivated behaviors. Thus, we have investigated the relationship between levels of generalized arousal and male sexual behaviors, hormone-dependent behaviors that have previously been shown to be affected by some of the same neurochemicals that are involved in CNS arousal (e.g., histamine and hypocretin) (21,22). We also used two assays of "anxiety," the elevated plus maze and the light/dark transition test, assuming that increases in anxiety would translate into decreases in exploration.…”

mentioning

confidence: 99%

Impact of generalized brain arousal on sexual behavior

Weil

Zhang

Hornung

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Although there is an extensive amount known about specific sensory and motor functions of the vertebrate brain, less is understood about the regulation of global brain states. We have recently proposed that a function termed generalized arousal (Ag) serves as the most elemental driving force in the nervous system, responsible for the initial activation of all behavioral responses. An animal with increased generalized CNS arousal is characterized by greater motor activity, increased responsivity to sensory stimuli, and greater emotional lability. Implicit in this theory was the prediction that increases in generalized arousal would augment specific motivated behaviors that depend on arousal. Here, we address the idea directly by testing two lines of mice bred for high or low levels of generalized arousal and assessing their responses in tests of specific forms of behavioral arousal, sex and anxiety/ exploration. We report that animals selected for differential generalized arousal exhibit marked increases in sensory, motor, and emotional reactivity in our arousal assay. Furthermore, male mice selected for high levels of generalized arousal were excitable and showed more incomplete mounts before the first intromission (IN), but having achieved that IN, they exhibited far fewer IN before ejaculating, as well as ejaculating much sooner after the first IN, thus indicating a high level of sexual arousal. Additionally, high-arousal animals of both sexes exhibited greater levels of anxiety-like behaviors and reduced exploratory behavior in the elevated plus maze and light-dark box tasks. Taken together, these data illustrate the impact of Ag on motivated behaviors.anxiety | behavioral genetics | generalized arousal | male sexual behavior O ne of the basic challenges facing all vertebrate animals is the necessity to activate large numbers of behavioral responses to large numbers of environmental conditions, some of which are threatening. We have recently proposed (1) that a function exists in vertebrate nervous systems that initiates behavioral activation of large numbers of responses to meet this basic challenge, a function we have termed generalized arousal. Neurons serving generalized arousal mechanisms would receive sensory inputs both from the external environment and the internal milieu and be able rapidly to activate arousal states that empower more specific, motivated behavioral responses. An increase in activity of this system would elevate generalized arousal, producing an animal with more motor activity, greater sensory responsiveness, and increased emotional lability. The purpose of the work reported here was to add to the evidence that a generalized arousal function exists (by beginning the breeding of high and low arousal lines of mice) and to test the impact of high or low generalized arousal states on specific motivated behaviors: male sexual behavior and anxiety/exploration.So far, the existence of generalized arousal as a measurable and physiologically-relevant CNS state has been inferred from three sepa...

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“…However, while Ox1R is highly selective for OxA, Ox2R binds both orexins with similar affinity. The hypothalamic orexins and their receptors are involved in the regulation of food intake (Sakurai 1999), sleep/wake cycle (Piper et al 2000), blood pressure and heart rate (Shirasaka et al 1999), sexual behaviour and arousal (Gulia et al 2003), plasma corticosterone levels (Kuru et al 2000), and adrenal and gonad functions (Barreiro et al 2004(Barreiro et al , 2005Martyńska et al 2006;Spinazzi et al 2006). A critical role of orexins and their cognate receptors in the pathogenesis of narcolepsy in mice and humans has been established (Chemelli et al 1999;Peyron et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Expression and role of receptor 1 for orexins in seminiferous tubules of rat testis

et al. 2012

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Orexins (OxA and OxB) and their receptors (Ox1R and Ox2R), originally detected in the hypothalamus, have also been localized in multiple cerebral areas and peripheral organs. Thus, in addition to their central function in the regulation of food intake, arterial blood pressure, heart rate, sleep/wake cycle, sexual behaviour, arousal, and hypothalamic/hypophyseal axis, these neuropeptides may exert a local action in various peripheral organs and tissues. Emerging evidence suggests a main role of OxA and its highly specific receptor Ox1R in the male genital tract of mammals. We previously demonstrated OxA localization in Sertoli cells and spermatids of rat testis. Here, we show positive stainings of Ox1R in developing spermatocytes, and spermatids of rat testis by immunohistochemistry. The expression of Ox1R mRNA and the protein in the tissue was also established by reverse-transcription polymerase chain reaction and Western blotting respectively. The addition of OxA to fresh testis slices significantly increased testosterone (T) secretion which, conversely, was inhibited by Mullerian inhibiting substance (MIS). The sequential treatment of testis samples with the two substances highlighted an antagonizing activity of OxA versus MIS in regulating T levels. Furthermore, the stimulating effect on T production by OxA was prevented by the addition of the selective Ox1R inhibitor SB-408124. Overall, our findings suggest that locally secreted OxA interacting with Ox1R activates signals which antagonize MIS action in the control of T levels in mammalian testis.

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Orexin A (hypocretin-1) application at the medial preoptic area potentiates male sexual behavior in rats

Cited by 80 publications

References 23 publications

A Role for Hypocretin (Orexin) in Male Sexual Behavior

A Role for Hypocretin (Orexin) in Male Sexual Behavior

Impact of generalized brain arousal on sexual behavior

Expression and role of receptor 1 for orexins in seminiferous tubules of rat testis

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