Lack of tolerance to the suppressing effect of rimonabant on chocolate intake in rats.
OBJECTIVE
Previous work indicated that tolerance to the anorectic effect of the cannabinoid CB1 receptor antagonist/inverse agonist, rimonabant, developed rather rapidly in rats and mice given access to a standard rodent chow. The present study was designed to investigate whether the reducing effect of rimonabant on intake of a highly palatable food such as a chocolate-flavoured beverage underwent a development of tolerance as rapid as that manifested on intake of a standard rodent chow.


METHODS
To this aim, Wistar rats were concurrently exposed, with unlimited access for 24 h/day, to the chocolate-flavoured beverage, regular food pellets and water. Rimonabant (0, 1.25, 2.5 and 5 mg/kg; i.p.) was administered once a day for 21 consecutive days.


RESULTS
Rimonabant administration resulted in a dose-dependent suppression of the high, daily intake of the chocolate-flavoured beverage; this effect lasted for the entire 21-day treatment period, without any apparent development of tolerance. Conversely, rimonabant-induced reduction in daily intake of regular food pellets was of a smaller magnitude and was limited to the first 3-4 days of treatment.


CONCLUSIONS
Together, these results indicate that chronically administered rimonabant was more effective and longer-lasting in reducing the intake of a highly palatable food than that of regular food pellets in rats. These results also suggest that rimonabant may be more active on the hedonic rather than nutritive properties of diets.
Gessa
Gian Luigi
GL
C.N.R. Institute of Neuroscience, Viale Diaz, 182, I-09126 Cagliari (CA), Italy.
Orrù
Alessandro
A
Lai
Paola
P
Maccioni
Paola
P
Lecca
Rossella
R
Lobina
Carla
C
Carai
Mauro A M
MA
Colombo
Giancarlo
G
D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001628:Beverages; D002099:Cacao; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D000077285:Rimonabant
D001067:Appetite Depressants; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant