Document Detail

Involvement of hypothalamic peptides in the anorectic action of the CB receptor antagonist rimonabant (SR 141716).
MedLine Citation:
PMID:  19490094     Owner:  NLM     Status:  In-Process    
Numerous studies have demonstrated that administration of rimonabant (SR 141716), a CB(1) receptor antagonist, causes a decrease in energy intake. However, the mechanisms by which rimonabant exerts its anorectic actions are unclear. The main focus of the study reported here was to establish the chemical identity of neurons that may subserve the anorectic effects of rimonabant. As such three approaches were utilised: (i) the identification of rimonabant-activated neurons using Fos as a marker of neuronal activity; (ii) the identification of the chemical phenotype of rimonabant-activated neurons by combining immunocytochemical identification of Fos and feeding-related peptides; and (iii) the evaluation of the effect of rimonabant on messenger RNA (mRNA) and protein for a number of feeding-related peptides. Rimonabant-induced Fos-positive nuclei were localized within a range of discrete hypothalamic regions with a predominance in the parvocellular part of the paraventricular nucleus of the hypothalamus, dorsomedial hypothalamus, arcuate nucleus and lateral hypothalamic area. Furthermore, Fos labelling within these hypothalamic regions was colocalized with anorexigenic and orexigenic peptides including melanin-concentrating hormone (MCH), orexin, cocaine- and amphetamine-regulated transcript (CART) and alpha-melanocyte-stimulating hormone (alpha-MSH). Rimonabant specifically induced a decrease in NPY and an increase in CART and alpha-MSH mRNA and protein, consistent with its effect in reducing food intake and increasing energy expenditure. As such these data provide insights into the mechanisms of action that may underpin rimonabant's effects on energy balance and body weight.
Aaron N A Verty; Wee M Boon; Paul E Mallet; Iain S McGregor; Brian J Oldfield
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-05-21
Journal Detail:
Title:  The European journal of neuroscience     Volume:  29     ISSN:  1460-9568     ISO Abbreviation:  Eur. J. Neurosci.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-08-07     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8918110     Medline TA:  Eur J Neurosci     Country:  France    
Other Details:
Languages:  eng     Pagination:  2207-16     Citation Subset:  IM    
Department of Physiology, Monash University, Clayton, VIC, Australia.
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