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

The nucleus accumbens and its related neural circuitry are known to be invo lved in mediating drug reward. The present brief review provides evidence t hat manipulation of the stimulus environment may alter the behavioral effec ts of drugs of abuse by altering accumbal circuitry. In experiments conduct ed in our laboratory, rats were raised in either an enriched condition (EC) or an impoverished condition (IC) and then were challenged with acute intr avenous amphetamine. EC rats were more sensitive than IC rats to the locomo tor stimulant effect of amphetamine, as well as to the accumbal dopamine re lease measured by in vivo microdialysis. No environment-induced difference in [H-3]-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 re lease, or dopamine autoreceptor sensitivity. Although the kinetic parameter s for [H-3]-dopamine uptake into striatal synaptosomes were not different b etween 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 t hat dopamine transporter proteins in the nucleus accumbens may be an import ant target for future studies aimed at identifying the cellular mechanism r esponsible for the environment-induced difference in the behavioral respons e to amphetamine.