Appetite-Suppressing Effects of Urocortin, a CRF-Related Neuropeptide

Spina, Mariarosa; Merlo‐Pich, Emilio; Chan, R.K.W.; Basso, Ana M.; Rivier, Jean; Vale, Wylie; Koob, George F.

doi:10.1126/science.273.5281.1561

Cited by 545 publications

(331 citation statements)

References 35 publications

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“…There is evidence that urocortins can act both centrally (Spina et al, 1996) and peripherally (Wang et al, 2001b) to elicit anoretic effects. The current studies highlight a hypothalamic site of action, but urocortins also may reduce feeding at other brain sites, as Ucn 1 previously potently induced anorexia following infusion into the caudal brainstem (Grill et al, 2000) or LS (Wang et al, 2001a).…”

Section: Discussionmentioning

confidence: 99%

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Delayed Satiety-Like Actions and Altered Feeding Microstructure by a Selective Type 2 Corticotropin-Releasing Factor Agonist in Rats: Intra-Hypothalamic Urocortin 3 Administration Reduces Food Intake by Prolonging the Post-Meal Interval

Fekete

Inoue

Zhao

et al. 2006

Neuropsychopharmacol

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Brain corticotropin-releasing factor/urocortin (CRF/Ucn) systems are hypothesized to control feeding, with central administration of 'type 2' urocortins producing delayed anorexia. The present study sought to identify the receptor subtype, brain site, and behavioral mode of action through which Ucn 3 reduces nocturnal food intake in rats. Non-food-deprived male Wistar rats (n ¼ 176) were administered Ucn 3 into the lateral (LV) or fourth ventricle, or into the ventromedial or paraventricular nuclei of the hypothalamus (VMN, PVN) or the medial amygdala (MeA), regions in which Ucn 3 is expressed in proximity to CRF 2 receptors. LV Ucn 3 suppressed ingestion during the third-fourth post-injection hours. LV Ucn 3 anorexia was reversed by cotreatment with astressin 2 -B, a selective CRF 2 antagonist and not observed following equimole subcutaneous or fourth ventricle administration. Bilateral intra-VMN and intra-PVN infusion, more potently than LV infusion, reduced the quantity (57-73%) and duration of ingestion (32-68%) during the third-fourth post-infusion hours. LV, intra-PVN and intra-VMN infusion of Ucn 3 slowed the eating rate and reduced intake by prolonging the post-meal interval. Intra-VMN Ucn 3 reduced feeding bout size, and intra-PVN Ucn 3 reduced the regularity of eating from pellet to pellet. Ucn 3 effects were behaviorally specific, because minimal effective anorectic Ucn 3 doses did not alter drinking rate or promote a conditioned taste aversion, and site-specific, because intra-MeA Ucn 3 produced a nibbling pattern of more, but smaller meals without altering total intake. The results implicate the VMN and PVN of the hypothalamus as sites for Ucn 3-CRF 2 control of food intake.

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Section: Discussionmentioning

confidence: 99%

“…Ucn 1 has greater CRF 2 affinity and more potently suppresses feeding than CRF, which led to the hypothesis that brain CRF 2 activation reduces food intake (Spina et al, 1996). Accordingly, CRF 2 deficiency, CRF 2 antisense, and CRF 2 antagonists attenuated intracerebroventricular (i.c.v.)…”

Section: Introductionmentioning

confidence: 99%

Delayed Satiety-Like Actions and Altered Feeding Microstructure by a Selective Type 2 Corticotropin-Releasing Factor Agonist in Rats: Intra-Hypothalamic Urocortin 3 Administration Reduces Food Intake by Prolonging the Post-Meal Interval

Fekete

Inoue

Zhao

et al. 2006

Neuropsychopharmacol

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“…It is generally acknowledged that icv administration of CRH-41 significantly reduces food intake while its effect on metabolism is mediated through activation of sympathetic nervous system (SNS) outflow and increased thermogenesis (Rothwell 1990, Spina et al 1996. Based on studies using a non-selective CRH antagonist it has been suggested that appetite reducing effect of emotional stress is conferred by CRH1R (Hotta et al 1999).…”

Section: The Integrated Stress Response-view From Crhmentioning

confidence: 99%

CRH: The link between hormonal-, metabolic- and behavioral responses to stress

Kovács

2013

Journal of Chemical Neuroanatomy

105

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Two major and mutually interconnected brain systems are recruited during stress reaction. One is the hypothalamic paraventricular nucleus (PVH) and the second is the extended amygdala. PVH governs the neuroendocrine stress response while CeA regulates most of the autonomic and behavioral stress reactions. The common neurohormonal mediator of these responses is the corticotropin-releasing hormone, CRH, which is expressed in both centers. CRH belongs to a larger family of neuropeptides that also includes urocortins 1, 2, and 3 all have different affinity towards the two types of CRHR receptors and have been implicated in regulation of stress and HPA axis activity. One functionally relevant aspect of CRH systems is their differential regulation by glucocorticoids. While corticosterone inhibits CRH transcription in the PVH, stress-induced glucocorticoids stimulate CRH expression in the extended amygdala. This review summarizes past and recent findings related to CRH gene regulation and its involvement in the neuroendocrine, autonomic and behavioral stress reaction.Key words: Corticotropin-releasing hormone, paraventricular nucleus, central amygdala, bed nucleus of stria terminalis, corticosterone, cAMP-response element.

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“…In addition to this role, CRF also acts as an extra-hypothalamic neuromodulator and neurotransmitter, mediating adaptive behavioral responses to stress, including increased arousal, suppression of appetitive and reproductive behaviors and an increase in defensive responding and avoidance behaviors (Brown and Fisher 1985;Dunn and Berridge 1990;Owens and Nemeroff 1993;Spina et al 1996;Spina et al 2000). These behavioral activating effects have been shown to be independent of HPA axis activation, and thus represent extra-hypothalamic actions of CRF in the CNS (Britton et al 1986;Eaves et al 1985).…”

Section: Introductionmentioning

confidence: 99%

Differential blockade of CRF-evoked behaviors by depletion of norepinephrine and serotonin in rats

et al. 2008

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Rationale-Central administration of corticotropin-releasing factor (CRF) elicits a specific pattern of behavioral responses resembling a stress-like state, and is anxiogenic in rodent models of anxiety.Objectives-Specific behaviors evoked by the administration of CRF were measured. The roles of CRF receptor subtypes and that of serotonergic and noradrenergic systems in mediating these responses were studied.Methods-Burying, grooming and head shakes were quantified in rats following intracerebroventricular administration of CRF and urocortin II and after pretreatment with antagonists. The role of forebrain norepinephrine in the behavioral responses to CRF (0.3 μg) was examined following pretreatment with the neurotoxin DSP-4 and that of serotonin after depletion using systemic administration of para-chlorophenylalanine (p-CPA).Results-CRF at 0.3 and 3.0 μg caused robust increases in burying, grooming and head shakes, but urocortin II was ineffective. Pretreatment with either antalarmin or propranolol significantly attenuated the CRF-evoked behaviors. Destruction of forebrain NE pathways blocked spontaneous burying behavior elicited by CRF and conditioned burying directed towards an electrified shock probe. In contrast, depletion of 5-HT selectively attenuated CRF-evoked grooming.Conclusions-Overt behavioral responses produced by CRF, burying, grooming, and head shakes, appeared to be mediated through the CRF 1 receptor. Spontaneous burying behavior evoked by CRF or conditioned burying directed towards a shock probe were disrupted by lesion of the dorsal noradrenergic bundle and may represent anxiety-like behavior caused by CRF activation of the LC. In contrast, CRF-evoked increases in grooming were dependent on serotonin.

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Appetite-Suppressing Effects of Urocortin, a CRF-Related Neuropeptide

Cited by 545 publications

References 35 publications

Delayed Satiety-Like Actions and Altered Feeding Microstructure by a Selective Type 2 Corticotropin-Releasing Factor Agonist in Rats: Intra-Hypothalamic Urocortin 3 Administration Reduces Food Intake by Prolonging the Post-Meal Interval

Delayed Satiety-Like Actions and Altered Feeding Microstructure by a Selective Type 2 Corticotropin-Releasing Factor Agonist in Rats: Intra-Hypothalamic Urocortin 3 Administration Reduces Food Intake by Prolonging the Post-Meal Interval

CRH: The link between hormonal-, metabolic- and behavioral responses to stress

Differential blockade of CRF-evoked behaviors by depletion of norepinephrine and serotonin in rats

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