Age-dependent effects of the cannabinoid CB1 antagonist SR141716A on food intake, body weight change, and pruritus in rats.
BACKGROUND
The cannabinoid CB1 selective antagonist SR141716A (Rimonabant) has been shown to decrease body weight in laboratory animals and humans. Furthermore, SR141716A can elicit scratching behavior in rodents, a behavior that has been hypothesized to contribute to SR141716A-induced decrease in food intake. Although childhood obesity is a rising health issue, it is unknown whether SR141716A is equipotent at modulating food intake and other CB1-mediated behaviors in younger subjects.


OBJECTIVE
To determine whether CB1 receptor blockade is equipotent at modulating food and water intake, body weight, and scratching behavior, the effect of a range of SR141716A doses on these behaviors in food-restricted postnatal day (P) 18, 28, and 60 male rats was investigated. Brain concentrations of SR141716A were determined in each age group.


RESULTS
SR141716A dose- and age-dependently suppressed food and water intake and body weight gain and elicited head scratching, with the most potent effects observed in P18 and P28 rats. Brain concentrations of SR141716A were significantly elevated in P18 rats relative to P28 and P60 rats. SR141716A-elicited head scratching was attenuated by the 5-HT(2A/2C) antagonist ketanserin.


CONCLUSIONS
SR141716A is more potent at modulating food intake and head scratching in very young animals; these differences can be attributed to an increase in brain penetration of SR141716A for P18 but not for P28 and P60 rats. In addition, SR141716-elicited head scratching is modulated by 5HT receptor antagonism and is not a contributing factor to SR141716A's anorectic effects.
Ward
Sara Jane
SJ
Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA 19140, USA. saraward@temple.edu
Lefever
Timothy W
TW
Rawls
Scott M
SM
Whiteside
Garth T
GT
Walker
Ellen A
EA
D000367:Age Factors; D000818:Animals; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects / Q000502:physiology; D004435:Eating / Q000187:drug effects* / Q000502:physiology / Q000523:psychology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology / Q000523:psychology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D010880:Piperidines / Q000493:pharmacokinetics / Q000494:pharmacology*; D011537:Pruritus / Q000209:etiology / Q000523:psychology*; D011720:Pyrazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D000077285:Rimonabant; D012702:Serotonin Antagonists / Q000494:pharmacology; D015430:Weight Gain / Q000187:drug effects* / Q000502:physiology
D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D012702:Serotonin Antagonists; D007650:Ketanserin; D000077285:Rimonabant