Dataset Information

Hypothalamic CRF1 receptor mechanisms are not sufficient to account for binge-like palatable food consumption in female rats.

ABSTRACT: OBJECTIVE:The present study evaluated the effect of systemic injection of the CRF1 receptor antagonist R121919, the corticosterone synthesis inhibitor metyrapone and central amygdala (CeA) injections of the nonselective CRF antagonist D-Phe-CRF(12-41) in rats in which binge eating was evoked by stress and cycles of food restriction. METHOD:Female rats were subjected or not to repeated cycles of regular chow food restriction/ad libitum feeding during which they were also given limited access (2 h) to palatable food. On the test day, rats were either exposed or not to the sight of the palatable food for 15 min without allowing access, before assessing food consumption. RESULTS:Systemic injections of R121919, but not of the metyrapone, blocked binge-like eating behavior. Restricted and stressed rats showed up-regulation of crh1 receptor mRNA signal in the bed nucleus of the stria terminalis and CeA but not in basolateral amygdala (BLA) or in the paraventricular nucleus. Injection D-Phe-CRF(12-41) in CeA but not in the BLA-blocked binge-like eating behavior. DISCUSSION:These findings demonstrate that extra-hypothalamic CRF1 receptors, rather than those involved in endocrine functions, are involved in binge eating and the crucial role of CRF receptors in CeA. CRF1 receptor antagonism may represent a novel pharmacological treatment for binge-related eating disorders.

SUBMITTER: Micioni Di Bonaventura MV

PROVIDER: S-EPMC5772704 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Hypothalamic CRF1 receptor mechanisms are not sufficient to account for binge-like palatable food consumption in female rats.

Micioni Di Bonaventura Maria Vittoria MV Ubaldi Massimo M Giusepponi Maria Elena ME Rice Kenner C KC Massi Maurizio M Ciccocioppo Roberto R Cifani Carlo C

The International journal of eating disorders 20170818 10

<h4>Objective</h4>The present study evaluated the effect of systemic injection of the CRF1 receptor antagonist R121919, the corticosterone synthesis inhibitor metyrapone and central amygdala (CeA) injections of the nonselective CRF antagonist D-Phe-CRF<sub>(12-41)</sub> in rats in which binge eating was evoked by stress and cycles of food restriction.<h4>Method</h4>Female rats were subjected or not to repeated cycles of regular chow food restriction/ad libitum feeding during which they were also ...[more]

PMID: 28833350

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Project description:RationaleBrain 5-HT2C receptors form part of a neural network that controls eating behaviour. 5-HT2C receptor agonists decrease food intake by activating proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus, but recent research in rodents has suggested that 5-HT2C receptor agonists may also act via dopaminergic circuitry to reduce the rewarding value of food and other reinforcers. No mechanistic studies on the effects of 5-HT2C agonists on food intake in humans have been conducted to date.ObjectivesThe present study examined the effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP) on food consumption, eating microstructure and blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) responses to food pictures in healthy female volunteers.MethodsIn a double-blind, placebo-controlled, crossover design, participants were randomized immediately after screening to receive oral mCPP (30mg) in a single morning dose, or placebo, in a counterbalanced order. Test foods were served from a Universal Eating Monitor (UEM) that measured eating rate and fMRI BOLD signals to the sight of food and non-food images were recorded.ResultsmCPP decreased rated appetite and intake of a palatable snack eaten in the absence of hunger but had no significant effect on the consumption of a pasta lunch (although pasta eating rate was reduced). mCPP also decreased BOLD fMRI responses to the sight of food pictures in areas of reward-associated circuitry. A post hoc analysis identified individual variability in the response to mCPP (exploratory responder-non-responder analysis). Some participants did not reduce their cookie intake after treatment with mCPP and this lack of response was associated with enhanced ratings of cookie pleasantness and enhanced baseline BOLD responses to food images in key reward and appetite circuitry.ConclusionsThese results suggest that 5-HT2C receptor activation in humans inhibits food reward-related responding and that further investigation of stratification of responding to mCPP and other 5-HT2C receptor agonists is warranted.

Dataset Information

Hypothalamic CRF1 receptor mechanisms are not sufficient to account for binge-like palatable food consumption in female rats.

Publications

Hypothalamic CRF1 receptor mechanisms are not sufficient to account for binge-like palatable food consumption in female rats.

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