Environmental Enrichment Reduces Methamphetamine Cue-induced Reinstatement but Does Not Alter Methamphetamine Reward or VMAT2 Function

Environmental factors influence a variety of health-related outcomes. In general, being raised in an environment possessing social, sensory, and motor enrichment reduces the rewarding effects of various drugs, thus protecting against abuse vulnerability. However, in the case of methamphetamine (METH), which acts at the vesicular monoamine transporter 2 (VMAT2) to enhance dopamine release from the cytosol, previous evidence suggests that METH reward may not be altered by environmental enrichment. This study examined the influence of an enriched environment on measures of METH reward, METH seeking, and VMAT2 function. Rats were raised from weaning to adulthood in either an enriched environment (presence of social cohorts and novel objects) or an isolated environment (no cohorts or novel objects). Rats in these two conditions were subsequently tested for their acquisition of conditioned place preference (CPP), METH self-administration, maintenance of self-administration at various unit doses of METH (0.001-0.5mg/kg/infusion), and cue-induced reinstatement. VMAT2 function in striatum from these two groups also was assessed. No significant environment effects were found in CPP or METH self-administration, which paralleled a lack of effect in VMAT2 function between groups. However, cue-induced reinstatement was reduced by environmental enrichment. Together, these results suggest that environmental enrichment does not alter VMAT2 function involved in METH reward. However, the enrichment-induced decrease in cue-induced reinstatement indicates that enrichment may have a beneficial effect against relapse following a period of extinction via a neural mechanism other than striatal VMAT2 function.