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Cannabinoid CB 2 receptor‐mediated regulation of impulsive‐like behaviour in DBA/2 mice
Author(s) -
Navarrete Francisco,
PérezOrtiz José M.,
Manzanares Jorge
Publication year - 2012
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2011.01542.x
Subject(s) - impulsivity , cannabinoid receptor type 2 , cannabinoid , medicine , nucleus accumbens , agonist , cannabinoid receptor , receptor , endocrinology , novelty seeking , psychology , neuroscience , chemistry , pharmacology , psychiatry , social psychology , personality , temperament
BACKGROUND AND PURPOSE This study evaluated gene expression differences between two mouse strains, characterized by opposite impulsivity‐like traits and the involvement of the cannabinoid CB 2 receptor in the modulation of impulsivity. EXPERIMENTAL APPROACH Behavioural tests were conducted to compare motor activity, exploration and novelty seeking, attention and cognitive and motor impulsivity (delayed reinforcement task: session duration 30 min; timeout 30 s) between A/J and DBA/2 mice. Expression of genes for dopamine D 2 receptors, CB 1 and CB 2 receptors were measured in the cingulate cortex (CgCtx), caudate‐putamen (CPu), accumbens (Acc), amygdala (Amy) and hippocampus (Hipp). Involvement of CB 2 receptors in impulsivity was evaluated in DBA/2 mice with a CB 2 receptor agonist (JWH133) and an antagonist (AM630). KEY RESULTS DBA/2 mice presented higher motor and exploratory activity, pre‐pulse inhibition impairment and higher cognitive and motor impulsivity level than A/J mice. In addition, DBA/2 mice showed lower (CgCtx, Acc, CPu) D 2 receptor, lower (Amy) and higher (CgCtx, Acc, CPu, Hipp) CB 1 receptor and higher (CgCtx, Acc, Amy) and similar (CPu, Hipp) CB 2 receptor gene expressions. Treatment with JWH133 (0.5, 1, 3 mg·kg −1 , i.p.) reduced cognitive and motor impulsivity level, accompanied by CB 2 receptor down‐regulation (CgCtx, Acc, Amy) but did not modify other behaviours. In contrast, AM630 (1, 2, 3 mg·kg −1 , i.p.) improved pre‐pulse inhibition and reduced novelty seeking behaviour in DBA/2 mice. CONCLUSIONS AND IMPLICATIONS CB 2 receptors might play an important role in regulating impulsive behaviours and should be considered a promising therapeutic target in the treatment of impulsivity‐related disorders.