title: Blockade by the cannabinoid CB1 receptor antagonist, rimonabant (SR141716), of the potentiation by quinelorane of food-primed reinstatement of food-seeking behavior.
abstract: It has been shown previously that the selective cannabinoid CB1 receptor antagonist, rimonabant (SR141716), reduced the intake of palatable food as well as the self-administration of several drugs of abuse, suggesting that endocannabinoid systems play a role in brain reward function. The present study investigated whether a cannabinoid step was involved in food-seeking behavior induced by explicit stimuli, using an operant reinstatement procedure in rats. Experimental sessions consisted of a 15-min food rewarded period, followed by a 45-min extinction period. Rimonabant did not affect the response reinstatement induced by noncontingent delivery of food pellets, but prevented (0.03-0.3 mg/kg) the potentiation by quinelorane, a dopamine D3 receptor-preferring agonist, of food-seeking behavior. A possible link between cannabinoid processes and D3- and/or D2-mediated dopaminergic transmission was further investigated by studying Fos protein expression in cortico-limbic structures in D3 (D3-/-) and D2 (D2-/-) knockout mice. Rimonabant (10 mg/kg) increased Fos immunoreactivity in the prefrontal cortex (pFCortex) and in the shell but not the core of the nucleus accumbens (NAcc). Fos induction by this dose of rimonabant was not seen in mice lacking CB1 receptors, providing clear evidence for the involvement of CB1 receptors. In the NAcc shell, the effect of rimonabant was suppressed in D3-/-, but remained unchanged in D2-/- mice. In contrast, Fos expression by rimonabant in the pFCortex was impervious to D2 or D3 receptor deletion. In conclusion, these data indicate first that rimonabant prevented the enhancement by quinelorane of the appetitive value of food pellets unexpectedly delivered during extinction and second that rimonabant effects might involve D3 receptor-mediated processes. Overall, these results are consistent with the notion that endocannabinoid functions control brain reward processes and in particular the capacity of explicit stimuli to precipitate food-seeking behavior.
authors.affiliation: 1INSERM U.288, Faculty of Medicine Pitié-Salpêtrière, Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Duarte
authors.forename: Richard
authors.initials: R
authors.lastname: Alonso
authors.forename: Nicole
authors.initials: N
authors.lastname: Bichet
authors.forename: Caroline
authors.initials: C
authors.lastname: Cohen
authors.forename: Philippe
authors.initials: P
authors.lastname: Soubrié
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Thiébot
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003463:Cues; D018491:Dopamine Agonists / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects*; D005260:Female; D005502:Food; D007150:Immunohistochemistry; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D011720:Pyrazoles / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology; D050637:Receptors, Dopamine D3; D000077285:Rimonabant
chemical_list: D018491:Dopamine Agonists; C493594:Drd3 protein, mouse; C493595:Drd3 protein, rat; D010880:Piperidines; D016760:Proto-Oncogene Proteins c-fos; D011720:Pyrazoles; D011804:Quinolines; D043884:Receptor, Cannabinoid, CB1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D000077285:Rimonabant; C047726:quinelorane