Abstract
Rationale and objectives
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.
Materials and 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.
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Acknowledgements
The authors are grateful to Mrs. Maria Elena Vincis for animal care and Ms. Anne Farmer for language editing of the manuscript. The present study was partially supported by Sanofi-Aventis, Milan, Italy.
All the experimental procedures employed in the present study were in accordance with the Italian Law on the “Protection of animals used for experimental and other scientific reasons”.
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Gessa, G.L., Orrù, A., Lai, P. et al. Lack of tolerance to the suppressing effect of rimonabant on chocolate intake in rats. Psychopharmacology 185, 248–254 (2006). https://doi.org/10.1007/s00213-006-0327-1
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DOI: https://doi.org/10.1007/s00213-006-0327-1