TY - JOUR PY - 2012// TI - Cannabinoid CB(2) receptor-mediated regulation of impulsive-like behaviour in DBA/2 mice JO - British journal of pharmacology A1 - Navarrete, Francisco A1 - Pérez-Ortiz, José M. A1 - Manzanares, Jorge SP - 260 EP - 273 VL - 165 IS - 1 N2 - Background and purpose: This study evaluated gene expression differences between two mouse strains characterised by opposite impulsivity-like traits and the involvement of the CB(2) cannabinoid receptor in the modulation of impulsivity. Experimental approach: Behavioural tests were conducted to characterise the differences in motor activity, exploration and novelty seeking, attention and cognitve and motor impulsivity (delayed reinforcement task: session duration 30 min; timeout 30 s) between A/J and DBA/2 mice. D(2) r, CB(1) r and CB(2) r gene expressions were measured in the cingulate cortex (CgCtx), caudate-putamen (CPu), accumbens (Acc), amygdala (Amy) and hippocampus (Hipp). Pharmacological manipulation with CB(2) r agonist (JWH133) and antagonist (AM630) was carried out in DBA/2 mice to evaluate the involvement of this receptor in impulsivity. Key results: Behavioural assessment showed that DBA/2 presented higher motor and exploratory activity, prepulse inhibition impairment and a higher cognitive and motor impulsivity level than A/J mice. In addition, DBA/2 showed lower (Cg Ctx, Acc, CPu) D(2) r, lower (Amy) and higher (Cg Ctx, Acc, CPu, Hipp) CB(1) r, and higher (Cg Ctx, Acc, Amy) and similar (CPu, Hipp) CB(2) r gene expressions. Pharmacological manipulation with JWH133 (0.5, 1, 3 mg·Kg(-1) , i.p.) reduced the cognitive and motor impulsivity level, effect that was accompanied by a CB(2) r down-regulation (Cg Ctx, Acc, Amy), but did not significantly modify other behaviours. In contrast, AM630 (1, 2, 3 mg·Kg(-1) , i.p.) significantly improved prepulse inhibition and reduced novelty seeking behaviour displayed by DBA/2 mice. Conclusions and implications: These results suggest that the CB(2) r might play an important role in the regulation of impulsive behaviours and should be considered a promising therapeutic target in the treatment of impulsivity-related disorders.
Language: en
LA - en SN - 0007-1188 UR - http://dx.doi.org/10.1111/j.1476-5381.2011.01542.x ID - ref1 ER -