Pretreatment with subeffective doses of Rimonabant attenuates orexigenic actions of orexin A-hypocretin 1.
Recent studies suggest that blockade of cannabinoid CB1 receptors suppresses feeding, an effect observed in humans treated with the cannabinoid CB1 antagonist Rimonabant. A cross-talk between cannabinoids and other systems controlling appetite might exist since cannabinoid receptors are present in hypothalamic neural circuits involved in feeding regulation and energy expenditure. Orexin A-hypocretin 1, an orexigenic peptide, is an ideal candidate to interact with cannabinoid receptors. Both of them play an important role in feeding and they co-localize in similar brain regions. To study this hypothesis we investigated (a) the effects on food intake of either orexin A-hypocretin 1 or the cannabinoid CB1 receptor antagonist Rimonabant in pre-fed rats, and (b) the interaction between them by monitoring the effects of the combined administration of cannabinoids and orexin A-hypocretin 1 in pre-fed rats. The results show that (1) orexin A-hypocretin 1 is a short-term modulator of appetite that increases food intake in pre-fed rats, (2) Rimonabant decreases food intake and (3) such effective and subeffective doses of Rimonabant block the orexigenic effect of orexin A-hypocretin 1. The results support the idea that cannabinoid and orexin A-hypocretin 1 systems share a common mechanism in food intake and indicate that the hypothalamic orexigenic circuits are involved in cannabinoid CB1 receptor antagonism-mediated reduction of appetite.
Crespo
Inmaculada
I
Departamento de Psicobiología, Facultad de Psicología, Universidad Complutense de Madrid, Campus de Somosaguas E-28223 Madrid, Spain.
Gómez de Heras
Raquel
R
Rodríguez de Fonseca
Fernando
F
Navarro
Miguel
M
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D063387:Cannabinoid Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects*; D005106:Exploratory Behavior / Q000187:drug effects*; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage*; D008297:Male; D009479:Neuropeptides / Q000008:administration & dosage*; D000068797:Orexins; D010880:Piperidines / Q000008:administration & dosage*; D011720:Pyrazoles / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D000077285:Rimonabant; D013997:Time Factors
D063387:Cannabinoid Receptor Antagonists; C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D010880:Piperidines; D011720:Pyrazoles; D000077285:Rimonabant