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Involvement of hypothalamic peptides in the anorectic action of the CB 1 receptor antagonist rimonabant (SR 141716)
Author(s) -
Verty Aaron N. A.,
Boon Wee M.,
Mallet Paul E.,
McGregor Iain S.,
Oldfield Brian J.
Publication year - 2009
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2009.06750.x
Subject(s) - rimonabant , anorectic , orexigenic , hypothalamus , endocrinology , medicine , ghrelin , orexin , antagonist , chemistry , receptor , biology , cannabinoid receptor , neuropeptide , hormone , neuropeptide y receptor , food intake
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 (α‐MSH). Rimonabant specifically induced a decrease in NPY and an increase in CART and α‐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.