Document Detail

Behavioral effects of CB2 cannabinoid receptor activation and its influence on food and alcohol consumption.
MedLine Citation:
PMID:  18991890     Owner:  NLM     Status:  MEDLINE    
Consumers of marijuana typically feel a strong, compulsive desire to consume food. Although past research revealed that the CB1 cannabinoid receptor is a potent regulator of food intake, the functional presence of neuronal CB2 cannabinoid receptors in the brain has been controversial. The role of CB2 receptors in food and alcohol consumption and the behavioral effects of CB2 receptor ligands are not well characterized. This is because CB2 cannabinoid receptors were thought to be absent from the brain and expressed primarily in immune cells and in the periphery. We tested the effects of peripheral injections of CB2 antagonist AM 630, CB2 agonist PEA, and CB1 antagonist AM 251 on male C57BL/6, Balb/c, and DBA/2 mice at the beginning of the night cycle and after overnight 12-hour fasts. We also investigated the effects of the putative CB2 agonist, JWH015, and CB2 antagonist, SR144528, in mouse motor function tests and in the two-compartment black and white box. Under standard conditions, the CB2 antagonist AM 630 inhibited food consumption in C57BL/6 mice and DBA/2 mice, but failed to block food intake of Balb/c mice. The CB2 agonist PEA had no significant effect on food consumption in Balb/c mice, and reduced food intake in C57BL/6 and DBA mice. The CB1 antagonist AM 251 inhibited food ingestion in the three mouse strains at variable times. After 12-hour food deprivation, the CB2 antagonist AM 630 increased food consumption in C57Bl/6 mice, but failed to produce significant changes in food intake for Balb/c and DBA/2 mice. The CB2 agonist PEA also reduced food consumption in all three mice strains at variable times. In comparison to the CB2 ligands, CB1 antagonist AM 251 inhibited food ingestion in the mouse strains. A general pattern of depression in locomotor activity was induced by JWH 015 in both males and females in the three mouse strains tested as the dose was increased. The development and enhancement of alcohol preference was observed after chronic treatment with CB2 agonist JWH 015 in stressed mice, but not in controls. In the DBA/2 strain, the spontaneous locomotor activity and stereotype behavior was enhanced by acute administration of low doses of SR144528. There was a reduction in CNR2 gene expression in the ventral mid-brain region of mice that developed alcohol preference, but not in those that did not develop alcohol preference. These effects of CB2 cannabinoid receptor ligands in in vivo behavioral tests are provided as functional evidence that CB2-Rs in the brain play a role in food and alcohol consumption and in the modification of mouse behavior.
E S Onaivi; O Carpio; H Ishiguro; N Schanz; G R Uhl; R Benno
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Annals of the New York Academy of Sciences     Volume:  1139     ISSN:  1749-6632     ISO Abbreviation:  Ann. N. Y. Acad. Sci.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-11-10     Completed Date:  2008-12-09     Revised Date:  2014-11-05    
Medline Journal Info:
Nlm Unique ID:  7506858     Medline TA:  Ann N Y Acad Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  426-33     Citation Subset:  IM    
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MeSH Terms
Alcohol Drinking*
Behavior, Animal / drug effects*
Cannabinoids* / metabolism,  pharmacology
Eating / drug effects*
Food Deprivation
Mice, Inbred Strains
Receptor, Cannabinoid, CB1 / antagonists & inhibitors,  metabolism
Receptor, Cannabinoid, CB2 / antagonists & inhibitors,  metabolism*
Grant Support
Z01 DA000165-13/DA/NIDA NIH HHS
Reg. No./Substance:
0/Cannabinoids; 0/Ligands; 0/Receptor, Cannabinoid, CB1; 0/Receptor, Cannabinoid, CB2

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