Document Detail


Control of food intake by MC4-R signaling in the lateral hypothalamus, nucleus accumbens shell and ventral tegmental area: interactions with ethanol.
MedLine Citation:
PMID:  22713514     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The melanocortin system is involved in animal models of obesity and anorexia-cachexia and MC4 receptors (MC4-R) are currently a target system for the development of drugs aimed to treat obesity and eating disorders in humans. Previous evidence suggest that feeding peptides might lack their orexigenic activity while stimulate ethanol intake. The present study comparatively evaluated food intake (4-h interval) in Sprague-Dawley (SD) rats drinking ethanol (6% w/v, 2 bottle choice paradigm) (EE group) and ethanol-naïve (EN) rats in response to bilateral infusion of the selective MC4-R antagonist HS014 (0, 0.02 or 0.05 μg/0.5 μl/site) or the selective MC4-R agonist cyclo(NH-CH(2)-CH(2)-CO-His-d-Phe-Arg-Trp-Glu)-NH(2) (0, 0.75 or 1.5 μg/0.5 μl/site), into the lateral hypothalamus (LH), the nucleus accumbens (NAc), or the ventral tegmental area (VTA). The main findings in the study are: (1) LH-infusions of the MC4-R antagonist increased and the agonist reduced feeding and total calories consumed, while ethanol intake remained unaltered. (2) NAc- and VTA-infusions of the selective agonist reduced food, ethanol and total calories intake. (3) NAc- and VTA-infusions of the MC4-R antagonist increased feeding in EN rats, but not in EE animals which showed a mild increase in ethanol intake, while total calories consumed remained unaltered. Present data show that having ethanol available reduces feeding elicited by NAc and VTA-MC4-R blockade. Additionally, while MC4-R signaling in the LH appears to modulate homeostatic aspects of feeding, it may contribute to non-homeostatic aspects of ingestive behaviors in the VTA and the NAc.
Authors:
Jose M Lerma-Cabrera; Francisca Carvajal; Lourdes de la Torre; Leticia de la Fuente; Montserrat Navarro; Todd E Thiele; Inmaculada Cubero
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-06-17
Journal Detail:
Title:  Behavioural brain research     Volume:  234     ISSN:  1872-7549     ISO Abbreviation:  Behav. Brain Res.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-07-30     Completed Date:  2012-12-07     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  8004872     Medline TA:  Behav Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  51-60     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier B.V. All rights reserved.
Affiliation:
Departamento de Neurociencia y Ciencias de Salud, Universidad de Almería, Almería, 04120, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / drug effects*,  metabolism
Eating / drug effects*
Ethanol / pharmacology*
Feeding Behavior / drug effects*
Hypothalamus / drug effects,  metabolism
Male
Nucleus Accumbens / drug effects,  metabolism
Rats
Rats, Sprague-Dawley
Receptor, Melanocortin, Type 4 / agonists,  antagonists & inhibitors,  metabolism
Signal Transduction / drug effects*
Ventral Tegmental Area / drug effects,  metabolism
Grant Support
ID/Acronym/Agency:
AA013573/AA/NIAAA NIH HHS; R01 AA013573/AA/NIAAA NIH HHS; R01 AA015148/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/Receptor, Melanocortin, Type 4; 64-17-5/Ethanol
Comments/Corrections

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