Decrease of glycogen synthase kinase 3I3 phosphorylation in the rat nucleus accumbens shell is necessary for amphetamine-induced conditioned locomotor activity

Abstract

Phosphorylation levels of glycogen synthase kinase 3I3 (GSK3I3) negatively correlated with psychomotor stimulant-induced locomotor activity. Locomotor sensitization induced by psychomotor stimulants was previously shown to selectively accompany the decrease of GSK3I3 phosphorylation in the nucleus accumbens (NAcc) core, suggesting that intact GSK3I3 activity in this region is necessary for psychomotor stimulants to produce locomotor sensitization. Similarly, GSK3I3 in the NAcc was also implicated in mediating the conditioned effects formed by the associations of psychomotor stimulants. However, it remains undetermined whether GSK3I3 plays a differential role in the two sub-regions (core and shell) of the NAcc in the expression of drug-conditioned behaviors. In the present study, we found that GSK3I3 phosphorylation was significantly lower in the NAcc shell obtained from rats expressing amphetamine (AMPH)-induced conditioned locomotor activity. Further, we demonstrated that these effects were normalized by treatment with lithium chloride, a GSK3I3 inhibitor. These results suggest that the behavior produced by AMPH itself and a conditioned behavior formed by associations with AMPH are differentially mediated by the two sub-regions of the NAcc.