Cannabinoid CB2 receptor-mediated regulation of impulsive-like behaviour in DBA/2 mice.

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 CB2 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 D2 receptors, CB1 and CB2 receptors were measured in the cingulate cortex (CgCtx), caudate-putamen (CPu), accumbens (Acc), amygdala (Amy) and hippocampus (Hipp). Involvement of CB2 receptors in impulsivity was evaluated in DBA/2 mice with a CB2 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) D2 receptor, lower (Amy) and higher (CgCtx, Acc, CPu, Hipp) CB1 receptor and higher (CgCtx, Acc, Amy) and similar (CPu, Hipp) CB2 receptor gene expressions. Treatment with JWH133 (0.5, 1, 3 mg·kg−1, i.p.) reduced cognitive and motor impulsivity level, accompanied by CB2 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 CB2 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. [ABSTRACT FROM AUTHOR]