Effects of SR141716A, a central cannabinoid receptor antagonist, on food-maintained responding.
Previous reports have indicated that administration of the central cannabinoid receptor (CB(1)) antagonist SR141716A decreases intake of highly palatable food and drink. Disruption of normal food intake has been reported only at high doses known to disrupt spontaneous behaviors. The present study was designed to determine if rates of responding for normal food were sensitive to the effects of cannabinoid receptor blockade. Adult, male Sprague-Dawley rats were trained to lever press for normal food pellets under a fixed-ratio 15 (FR 15) schedule of reinforcement. SR141716A (0.3-3.0 mg/kg) produced dose-dependent reductions in response rate. WIN 55,212-2 (0. 3 mg/kg), a high efficacy cannabinoid agonist, given as a pre-treatment to SR141716A, significantly attenuated the rate-suppressing effects of SR141716A, suggesting a principal role of CB(1) receptors in mediating these behavioral effects. These data indicate that high palatability is not necessary to observe an anorectic effect of SR141716A.
Freedland
C S
CS
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
Poston
J S
JS
Porrino
L J
LJ
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D048588:Benzoxazines; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects; D004435:Eating / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists / Q000037:antagonists & inhibitors*; D000077285:Rimonabant
D048588:Benzoxazines; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D000077285:Rimonabant