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Int J Neuropsychopharmacol ; 13(9): 1247-54, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20663269

RESUMO

The central nervous system control of food intake has been extensively studied, hence, several neurotransmitter systems regulating this function are now clearly identified, for example, the endocannabinoid and serotoninergic systems. The former stimulates feeding while the latter inhibits it. Oleamide (Ole) is a cannabimimetic molecule affecting both systems. In this work, we tested the orexigenic and anorectic potential of Ole when administered into the nucleus accumbens shell (NAcS), a brain region that has been related to the orexigenic effects of cannabinoids. Additionally, we tested if Ole administered into this nucleus affects the activity of the hypothalamic nuclei involved in feeding behaviour, just as other cannabinoids do. We found a hyperphagic effect of Ole that is mediated through CB1 activation. The combination of Ole and the CB1 antagonist, AM251, produced a hypophagia that was fully blocked by SB212084, a 5-HT2C receptor antagonist. We also show that blockade of 5-HT2C and 5-HT2A receptors in the NAcS stimulates food intake. Finally, the combination of Ole and AM251 activates hypothalamic nuclei, an effect also blocked by SB242084. In conclusion, we show, for the first time, that Ole administered into the NAcS has a dual effect on feeding behaviour, acting through cannabinoid and serotonin receptors. These effects probably result from a downstream interaction with the hypothalamus.


Assuntos
Ingestão de Alimentos/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Núcleo Accumbens/efeitos dos fármacos , Ácidos Oleicos/farmacologia , Receptor CB1 de Canabinoide/metabolismo , Antagonistas do Receptor 5-HT2 de Serotonina/farmacologia , Aminopiridinas/farmacologia , Animais , Comportamento Alimentar/fisiologia , Hiperfagia/induzido quimicamente , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Indóis/farmacologia , Ketanserina/farmacologia , Masculino , Atividade Motora/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Ácidos Oleicos/administração & dosagem , Piperidinas/farmacologia , Pirazóis/farmacologia , Ratos , Ratos Wistar , Receptor CB1 de Canabinoide/antagonistas & inibidores , Receptor CB1 de Canabinoide/biossíntese , Receptor 5-HT2A de Serotonina/metabolismo , Receptor 5-HT2C de Serotonina/metabolismo
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