Document Detail

Voluntary exercise augments acute effects of CB1-receptor inverse agonist on body weight loss in obese and lean mice.
MedLine Citation:
PMID:  14724049     Owner:  NLM     Status:  MEDLINE    
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.
Dan Zhou; Lauren P Shearman
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  Pharmacology, biochemistry, and behavior     Volume:  77     ISSN:  0091-3057     ISO Abbreviation:  Pharmacol. Biochem. Behav.     Publication Date:  2004 Jan 
Date Detail:
Created Date:  2004-01-15     Completed Date:  2004-09-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0367050     Medline TA:  Pharmacol Biochem Behav     Country:  United States    
Other Details:
Languages:  eng     Pagination:  117-25     Citation Subset:  IM    
Department of Pharmacology, Merck Research Laboratories, RY80Y-150, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA.
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MeSH Terms
Body Weight / drug effects,  physiology
Dose-Response Relationship, Drug
Eating / drug effects,  physiology
Mice, Inbred C57BL
Mice, Obese
Physical Conditioning, Animal / physiology*
Piperidines / pharmacology,  therapeutic use
Pyrazoles / pharmacology,  therapeutic use
Receptor, Cannabinoid, CB1 / agonists*,  antagonists & inhibitors,  physiology*
Thinness / physiopathology*
Weight Loss / drug effects*,  physiology*
Reg. No./Substance:
0/AM 251; 0/Piperidines; 0/Pyrazoles; 0/Receptor, Cannabinoid, CB1

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