| Methamphetamine is a potent stimulant of the central nervous system widely abused in the United States and many other countries. Methamphetamine abusers who self-administer frequent high doses of methamphetamine, such as cyclic users, may be susceptible to methamphetamine-induced neurotoxicity. Research using the environmental enrichment paradigm indicates that rats raised in an enriched environment show protection against the behavioral consequences of some types of brain injury. The current study investigated the effects of environmental enrichment on methamphetamine-induced decreases in evoked dopamine release, depletions of monoamines and metabolites in brain tissue, and changes in locomotor activity and subsequent methamphetamine reward as measured by conditioned place preference (CPP). Male Sprague-Dawley rats were raised in either an enriched or isolated condition from 21 to 55 days of age, and then were placed in a standard housing condition for the remainder of the experiment. At 56 days of age, rats received injections of either 10 mg/kg methamphetamine or saline every 2 hours for a total of 4 injections. Colonic body temperatures were measured hourly during methamphetamine treatment. Microdialysis was conducted in awake rats two-weeks after treatment to measure potassium- and methamphetamine-evoked overflow of dopamine and its metabolites in the striatum. Tissue levels of dopamine, serotonin, and metabolites were measured in the striatum, nucleus accumbens, and prefrontal cortex at the end of each experiment. For the CPP experiment, rats were conditioned with methamphetamine (0.3 or 1.0 mg/kg) or saline using a 4-trial CPP procedure. Potassium-evoked dopamine overflow was decreased in both EC and IC methamphetamine-treated rats compared to saline controls, while methamphetamine-evoked dopamine overflow was decreased in only EC methamphetamine-treated rats. Additionally, EC rats treated with neurotoxic doses of methamphetamine showed a greater decrease in basal DOPAC and HVA levels and a greater decrease in tissue concentration of dopamine in Nacc compared to IC rats. For locomotor activity, methamphetamine-treated EC rats conditioned with 1 mg/kg methamphetamine showed more pronounced hyperactivity compared to methamphetamine-treated IC rats. These results suggest that EC rats may be more vulnerable than IC rats to the neurochemical and behavioral consequences of methamphetamine neurotoxicity. |
