Voluntary exercise augments acute effects of CB1-receptor inverse agonist on body weight loss in obese and lean mice

Cannabinoid CB1 receptor (CB1R) inverse agonists reduce appetite and body weight (BW) gain in various species. Exercise is thought to be a natural reward process and the cannabinoid system is also believed to influence reward. We tested the hypothesis that voluntary exercise would augment the effect...

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Bibliographic Details
Published in:Pharmacology, biochemistry and behavior biochemistry and behavior, 2004, Vol.77 (1), p.117-125
Main Authors: Zhou, Dan, Shearman, Lauren P.
Format: Article
Language:English
Subjects:
Agouti mice
Animals
Biological and medical sciences
Body Weight - drug effects
Body Weight - physiology
Cannabinoid
Dose-Response Relationship, Drug
Eating - drug effects
Eating - physiology
Female
Food intake
Fundamental and applied biological sciences. Psychology
Medical sciences
Mice
Mice, Inbred C57BL
Mice, Obese
Neuropharmacology
ob/ob mice
Obesity
Pharmacology. Drug treatments
Physical Conditioning, Animal - physiology
Piperidines - pharmacology
Piperidines - therapeutic use
Psychology. Psychoanalysis. Psychiatry
Psychology. Psychophysiology
Pyrazoles - pharmacology
Pyrazoles - therapeutic use
Receptor, Cannabinoid, CB1 - agonists
Receptor, Cannabinoid, CB1 - antagonists & inhibitors
Receptor, Cannabinoid, CB1 - physiology
Running wheels
Thinness - physiopathology
Weight Loss - drug effects
Weight Loss - physiology
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Summary:Cannabinoid CB1 receptor (CB1R) inverse agonists reduce appetite and body weight (BW) gain in various species. Exercise is thought to be a natural reward process and the cannabinoid system is also believed to influence reward. We tested the hypothesis that voluntary exercise would augment the effects of AM251, a CB1R inverse agonist, on food intake (FI) and BW loss in murine genetic models of obesity. ob/ob, agouti yellow (A y), and lean C57BL/6J mice were treated via oral gavage with vehicle or AM251 (1, 3, or 10 mg/kg) 1 h before the dark cycle. The suppressive effects of 3 and 10 mg/kg AM251 on overnight FI, BW gain, and water intake (WI) were significant in ob/ob mice. In contrast, in A y mice, 10 mg/kg AM251 decreased FI and BW gain while it did not influence WI. Food consumption of ob/ob and A y mice, as evidenced by feeding frequency (FF) and feeding duration (FD), was reduced by AM251 for 4–6 h. AM251 at these doses had no impact on the appetitive behavior or BW gain of lean mice. After a 1-week wash-out period, mice were given running wheels in their home cages. With running wheel exercise, lean and obese mice exhibited increased sensitivity to AM251. Low voluntary wheel running activity of ob/ob mice precluded detection of combined effects of AM251 and exercise in this genetic model of obesity. Lean and agouti mice given AM251 combined with exercise lost a greater amount of BW than with AM251 alone. Our data suggest that voluntary exercise can enhance CB1R inverse agonist effects on appetite and BW loss in both lean and agouti obese mice.
ISSN:0091-3057
1873-5177
DOI:10.1016/j.pbb.2003.10.015