Centrally administered orexin-A activates corticotropin-releasing factor-containing neurons in the hypothalamic paraventricular nucleus and central amygdaloid nucleus of rats: possible involvement of central orexins on stress-activated central CRF neurons

Sakamoto, Fumihiko; Yamada, Seiji; Ueta, Yoichi

doi:10.1016/j.regpep.2003.12.014

Cited by 146 publications

(108 citation statements)

References 34 publications

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“…OX neurons in the perifornical-dorsomedial hypothalamus have been proposed to mediate stress activation (Harris and Aston-Jones, 2006, for a review, see Koob, 2008). Possibly, OXA from this hypothalamic area activates CRF-expressing neurons in the paraventricular nucleus of the hypothalamus and in the central nucleus of the amygdala (Sakamoto et al, 2004). Accordingly, OX 1 R antagonists inhibit reinstatement of ethanol and sucrose seeking induced by the pharmacological stressor yohimbine (Richards et al, 2008) and OXA reinstates cocaine-seeking behavior (Boutrel et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Role of Orexin-1 Receptor Mechanisms on Compulsive Food Consumption in a Model of Binge Eating in Female Rats

Piccoli

Bonaventura

Cifani

et al. 2012

Neuropsychopharmacol

144

102

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Orexins (OX) and their receptors (OXR) modulate feeding, arousal, stress, and drug abuse. Neural systems that motivate and reinforce drug abuse may also underlie compulsive food seeking and intake. Therefore, the effects of GSK1059865, a dual OX 1 /OX 2 R antagonist were evaluated in a binge eating (BE) model in female rats. BE of highly palatable food (HPF) was evoked by three cycles of food restriction followed by stress, elicited by exposing rats to HPF, but preventing them from having access to it for 15 min. Pharmacokinetic assessments of all compounds were obtained under the same experimental conditions used for the behavioral experiments. Topiramate was used as the reference compound as it selectively blocks BE in rats and humans. Dose-related thresholds for sleep-inducing effects of the OXR antagonists were measured using polysomnography in parallel experiments. SB-649868 and GSK1059865, but not JNJ-10397049, selectively reduced BE for HPF without affecting standard food pellet intake, at doses that did not induce sleep. These results indicate, for the first time, a major role of OX 1 R mechanisms in BE, suggesting that selective antagonism at OX 1 R could represent a novel pharmacological treatment for BE and possibly other eating disorders with a compulsive component.

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Section: Discussionmentioning

confidence: 99%

Role of Orexin-1 Receptor Mechanisms on Compulsive Food Consumption in a Model of Binge Eating in Female Rats

Piccoli

Bonaventura

Cifani

et al. 2012

Neuropsychopharmacol

144

102

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“…Pharmacological administration of synthetic orexin in rats resulted in increased release of ACTH and PRL (1,5,13,14,27,28,32), and it is clear that the ability of orexin to stimulate the HPA axis is due primarily to an action in the brain that causes release of corticotrophin-releasing factor (CRF) into the median eminence (and subsequent diffusion into the hypophyseal portal vessels for access to the corticotrophs of the anterior pituitary gland) from parvocellular neurons located in the PVN (1, 13, 14, 27, 28, 32). If this pharmacological action of exogenously administered orexin has physiological relevance, then antagonism of the actions of the endogenous peptide should alter the HPA axis response to physiological stressors.…”

Section: Discussionmentioning

confidence: 99%

“…We hypothesize that CRFproducing parvocellular cells in the PVN express the OX 1 R and that endogenous orexin controls the activity of those neurons during immobilization stress. Indeed, immobilization stress resulted in increased Fos immunoreactivity in orexin neurons (28), and orexin administration induced expression of the c-fos gene and Fos protein in parvocellular neurons of the PVN (18). We anticipate that future singlecell RT-PCR experiments will allow us to directly identify the phenotype of the neurons in the PVN that responds to orexin and, thus, determine whether the stimulation of ACTH secretion in vivo is the result of orexin action directly on CRF-producing cells or interneurons within the PVN.…”

Section: Discussionmentioning

confidence: 99%

Hypocretin/orexin type 1 receptor in brain: role in cardiovascular control and the neuroendocrine response to immobilization stress

Samson

Bagley²,

Ferguson³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Samson WK, Bagley SL, Ferguson AV, White MM. Hypocretin/ orexin type 1 receptor in brain: role in cardiovascular control and the neuroendocrine response to immobilization stress. Am J Physiol Regul Integr Comp Physiol 292: R382-R387, 2007. First published August 10, 2006; doi:10.1152/ajpregu.00496.2006.-Hypocretin/orexin acts pharmacologically in the hypothalamus to stimulate stress hormone secretion at least in part by an action in the hypothalamic paraventricular nucleus, where the peptide's receptors have been localized. In addition, orexin acts in the brain to increase sympathetic tone and, therefore, mean arterial pressure and heart rate. We provide evidence for the role of endogenously produced hypocretin/orexin in the physiological response to immobilization stress and identify the receptor subtype responsible for this action of the peptide. Antagonism of the orexin type 1 receptor (OX 1R) in the brain prevented the ACTHstimulating effect of centrally administered hypocretin/orexin. Furthermore, pretreatment of animals with the OX 1R antagonist blocked the ACTH response to immobilization/restraint stress. The OX 1R antagonist did not, however, block the pharmacological or physiological release of prolactin in these two models. Antagonism of the OX 1R also blocked the central action of orexin to elevate mean arterial pressures and heart rates in conscious rats. These data suggest receptor subtype-selective responses to hypocretin/orexin and provide further evidence for the importance of endogenously produced peptide in the physiological control of stress hormone secretion. autonomic function; hypothalamus; adrenocorticotropin; prolactin IN ADDITION TO THE WELL-CHRONICLED pharmacological actions of the hypocretins/orexins on arousal state (6,23,29,36), the peptides (referred to here simply as orexins) exert a variety of behavioral (24), autonomic (7,15,34), and endocrine (1, 5, 7, 13, 22, 26 -28, 31, 32) actions mediated by the two characterized binding proteins, the orexin type 1 (OX 1 R) and the orexin type 2 (OX 2 R) receptors (29). Although orexin A and orexin B have many common pharmacological effects, some actions unique to one and not the other have been reported (7,36). Since orexin A binds with higher affinity to the OX 1 R than orexin B and both isoforms bind with apparently equal affinity to the OX 2 R, many investigators have narrowed their attention to the pharmacological effects of orexin A. Our original studies focused on endocrine, cardiovascular, and behavioral actions of orexin A in the hypothalamus and brain stem (7,32,37,38). We demonstrated direct neuronal actions of orexin in the hypothalamic paraventricular nucleus (PVN) and established that the action of exogenous orexin to stimulate the hypothalamic-pituitary-adrenal (HPA) axis was mediated at least in part by the release of corticotrophin-releasing hormone (CRH) (32). We have attempted to identify the receptor subtype responsible for the cardiovascular and neuroendocrine actions of these peptides and provide evidence for the i...

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“…Second, we used transgenic mice (orexin/YC2.1) in which Hcrt neurons specifically express the yellow cameleon calcium-sensing protein (24). Ca 2+ imaging of Hcrt neurons from these mice revealed that N/OFQ inhibited intracellular Ca 2+ concentration in 18 of 28 of the Hcrt neurons tested ( Figure 3E); this effect was concentration dependent, with an EC 50 of approximately 50 nM ( Figure 3F).…”

Section: Introductionmentioning

confidence: 99%

Hypocretin/orexin and nociceptin/orphanin FQ coordinately regulate analgesia in a mouse model of stress-induced analgesia

Xie

Wisor²,

Hara³

et al. 2008

J. Clin. Invest.

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Centrally administered orexin-A activates corticotropin-releasing factor-containing neurons in the hypothalamic paraventricular nucleus and central amygdaloid nucleus of rats: possible involvement of central orexins on stress-activated central CRF neurons

Cited by 146 publications

References 34 publications

Role of Orexin-1 Receptor Mechanisms on Compulsive Food Consumption in a Model of Binge Eating in Female Rats

Role of Orexin-1 Receptor Mechanisms on Compulsive Food Consumption in a Model of Binge Eating in Female Rats

Hypocretin/orexin type 1 receptor in brain: role in cardiovascular control and the neuroendocrine response to immobilization stress

Hypocretin/orexin and nociceptin/orphanin FQ coordinately regulate analgesia in a mouse model of stress-induced analgesia

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