Document Detail

The neutral cannabinoid CB₁ receptor antagonist AM4113 regulates body weight through changes in energy intake in the rat.
MedLine Citation:
PMID:  21056053     Owner:  NLM     Status:  MEDLINE    
The aim of this study was to determine if the neutral cannabinoid CB₁ receptor antagonist, AM4113, regulates body weight in the rat via changes in food intake. We confirmed that the AM4113-induced reduction in food intake is mediated by CB₁ receptors using CB₁ receptor knockout mice. In rats, intraperitoneally administered AM4113 (2, 10 mg kg⁻¹) had a transient inhibitory effect on food intake, while body weight gain was suppressed for the duration of the study. AM4113-induced hypophagia was no longer observed once the inhibitory effect of AM4113 on body weight stabilized, at which time rats gained weight at a similar rate to vehicle-treated animals, yet at a lower magnitude. Pair-feeding produced similar effects to treatment with AM4113. Food intake and body weight gain were also inhibited in rats by oral administration of AM4113 (50 mg kg⁻¹). Dual energy x-ray absorptiometry (DEXA) was used to measure lean and fat mass. The AM4113 treated group had 29.3±11.4% lower fat mass than vehicle-treated rats; this trend did not reach statistical significance. There were no differences in circulating levels of the endogenous cannabinoid 2-arachidonoyl glycerol (2-AG), glucose, triglycerides, or cholesterol observed between treatment groups. Similarly, 2-AG hypothalamic levels were not modified by AM4113 treatment. These data suggest that blockade of an endocannabinoid tone acting at CB₁ receptors induces an initial, transient reduction in food intake which results in long-term reduction of body weight gain.
Nina L Cluny; Adam P Chambers; V Kiran Vemuri; Jodianne T Wood; Lindsay K Eller; Carmelina Freni; Raylene A Reimer; Alexandros Makriyannis; Keith A Sharkey
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-11-04
Journal Detail:
Title:  Pharmacology, biochemistry, and behavior     Volume:  97     ISSN:  1873-5177     ISO Abbreviation:  Pharmacol. Biochem. Behav.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-14     Completed Date:  2011-04-11     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  0367050     Medline TA:  Pharmacol Biochem Behav     Country:  United States    
Other Details:
Languages:  eng     Pagination:  537-43     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
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MeSH Terms
Absorptiometry, Photon
Body Weight / drug effects*
Energy Metabolism / drug effects*
Pyrazoles / administration & dosage,  pharmacology*
Rats, Sprague-Dawley
Receptor, Cannabinoid, CB1 / antagonists & inhibitors*
Grant Support
DA09158/DA/NIDA NIH HHS; DA3801/DA/NIDA NIH HHS; DA7215/DA/NIDA NIH HHS; P01 DA009158/DA/NIDA NIH HHS; P01 DA009158-12/DA/NIDA NIH HHS; R01 DA007215/DA/NIDA NIH HHS; R01 DA007215-16/DA/NIDA NIH HHS; R37 DA003801/DA/NIDA NIH HHS; R37 DA003801-22/DA/NIDA NIH HHS; //Canadian Institutes of Health Research
Reg. No./Substance:
0/AM4113; 0/Pyrazoles; 0/Receptor, Cannabinoid, CB1

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