Cannabinoid CB 2 receptor-mediated regulation of impulsive-like behaviour in DBA/2 mice

Abstract

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. © 2011 The British Pharmacological Society.