Behavioral mechanisms underlying inhibition of food-maintained responding by the cannabinoid receptor antagonist/inverse agonist SR141716A.
This study investigated the possible behavioral mechanisms underlying the anorectic effect of the cannabinoid CB(1) receptor antagonist/inverse agonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A). Male or female rats were food-restricted and trained to emit stable responding in daily 10-min, fixed ratio 10 food-reinforced operant sessions. Under these conditions, as well as under free-feeding conditions, SR141716A inhibited food-maintained responding (ED(50) values ranging from 0.92 to 2.52 mg/kg, i.p.). In the same operant procedure, SR141716A suppressed intracranial self-stimulation with a potency which was slightly lower than the anorectic potency (ED(50): 4.50 mg/kg). As assessed during a 10-min test period SR141716A (1-10 mg/kg) did not affect activity counts; suggesting that the observed inhibition of operant behavior is not a direct consequence of impairment of locomotor activity. SR141716A, however, attenuated saccharin-preference in a conditioned taste aversion paradigm (ED(50): 6.45 mg/kg). Although the data support the suggestion that the anorectic effect of SR141716A results from an attenuating effect on the rewarding effect of food, the contribution of drug-induced aversion/malaise cannot be excluded.
De Vry
Jean
J
CNS Research, Bayer HealthCare, Aprather Weg 18a, 42096 Wuppertal, Germany. jean.vry.jv1@bayer-ag.de
Schreiber
Rudy
R
Eckel
Gisela
G
Jentzsch
Klaus Rüdiger
KR
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005260:Female; D005502:Food; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000077285:Rimonabant; D012653:Self Stimulation; D013649:Taste / Q000187:drug effects
D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D010880:Piperidines; D011720:Pyrazoles; D000077285:Rimonabant