Issn Print: 0955-8810

Publication Date: 2005/09/01


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B6 EFFECT OF SR141716A IN FEEDING REGULATION AND ITS INTERACTION WITH OREXIN A

I. Crespo; R. Gómez; G. González-Cuevas; J.A. López-Moreno; G. Moreno; M. Navarro

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The cannabinoid system is involved in feeding regulation through the CB1 receptor, a G-protein-coupled receptor (GPCR). SR141716A, a selective central cannabinoid (CB1) receptor antagonist, blocks the hyperphagia induced by cannabinoids. A biochemical interaction between CB1 and OXR1, an orexin receptor, has been found in a recent in vitro study. Furthermore, CB1 and OX1R receptors are co-expressed in the lateral hypothalamus.
For further investigation of the in vivo interaction between orexin A and cannabinoids in feeding behavior, we have studied: (1) the effect of peripheral administration of SR141716A; (2) the effect of central administration of orexin A; and (3) the effect of combined administration of SR141716A and orexin A, all in pre-fed animals.
Male Wistar rats were used in two groups. In the first one, the acute effect on feeding of three different doses of i.p. SR141716A was measured. In the second group, SR141716A (1 mg/kg) was injected i.p. and, 10 min later, orexin A was injected i.c.v. in pre-fed rats. Food intake was measured every 60 min for 240 min. Body weight and water intake was measured before the test and 240 min afterwards.
Systemic administration of the selective CB1 antagonist SR141716A reduced food intake, water intake and body weight. Administration of orexin A increased feeding in pre-fed animals at 60 min after i.c.v. injection at every dose, and SR141716A blocked the effect of orexin A on food and water intake in partially satiated rats.
This research studies the connections between the cannabinoid system and orexin A in vivo for the first time. The results obtained provide evidence of the existence of a relationship between them and confirm the in vitro results of Hilairet et al. (J Biol Chem278:23731–23737, 2003). SR141716A blocks the orexigenic effect of orexin A and it is a new therapeutic target of different feeding diseases.
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