Environmental enrichment enhances the stimulant effect of intravenous amphetamine: Search for a cellular mechanism in the nucleus accumbens

Abstract

The nucleus accumbens and its related neural circuitry are known to be involved in mediating drug reward. The present brief review provides evidence that manipulation of the stimulus environment may alter the behavioral effects of drugs of abuse by altering accumbal circuitry. In experiments conducted in our laboratory, rats were raised in either an enriched condition (EC) or an impoverished condition (IC) and then were challenged with acute intravenous amphetamine. EC rats were more sensitive than IC rats to the locomotor stimulant effect of amphetamine, as well as to the accumbal dopamine release measured by in vivo microdialysis. No environment-induced difference in [3H]-amphetamine pharmacokinetics was observed. In vitro neurochemical experiments also indicated that accumbal tissue slices isolated from EC and IC rats did not differ in dopamine levels, electrically evoked dopamine release, or dopamine autoreceptor sensitivity. Although the kinetic parameters for [3H]-dopamine uptake into striatal synaptosomes were not different between EC and IC rats, the transport inhibitor GBR 12935 was more potent in inhibiting uptake in EC rats than in IC rats. The latter results suggest that dopamine transporter proteins in the nucleus accumbens may be an important target for future studies aimed at identifying the cellular mechanism responsible for the environmentinduced difference in the behavioral response to amphetamine.