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 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.