Citation

Navarrete F, Pérez-Ortiz JM, Manzanares J. Br. J. Pharmacol. 2012; 165(1): 260-273.

Affiliation

Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Avda. Ramón y Cajal s/n San Juan de Alicante, 03550 Alicante, Spain, and Unidad de Neuropsicofarmacología Traslacional, Complejo Hospitalario Universitario de Albacete, C/ Hermanos Falcó 37, Albacete 02006, Spain.

Copyright

(Copyright © 2012, John Wiley and Sons)

DOI

10.1111/j.1476-5381.2011.01542.x

PMID

21671903

PMCID

PMC3252982

Abstract

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