Methamphetamine-induced neurotoxicity alters locomotor activity, stereotypic behavior, and stimulated dopamine release in the rat

The neurochemical evidence of methamphetamine (MA) induced toxicity to dopa minergic nerve terminals is well documented; however, the functional conseq uences are not clearly defined. The present study was designed to investiga te whether MA-induced dopamine depletions affect locomotor activity, stereo typic behavior, and/or extracellular dopamine concentrations in the neostri atum. Male rats were treated with a neurotoxic regimen of MA (10 mg/kg, i.p ., every 2 hr for four injections) or vehicle and tested for functional eff ects 1 week later. Animals that had received the neurotoxic regimen of MA s howed a reduction in both caudate nucleus and nucleus accumbens dopamine co ntents of 56 and 30%, respectively. Furthermore, MA-treated rats exhibited a significant attenuation in spontaneous activity, as well as a significant diminution in MA (low dose)-stimulated locomotor activity as compared to v ehicle-treated rats. However, there were no differences in the MA (low dose )-induced increases in extracellular dopamine concentrations in the caudate nucleus or the nucleus accumbens core of either group. Interestingly, the acute administration of higher doses of MA elicited a significantly augment ed stereotypic response and a significantly attenuated increase in the extr acellular concentration of dopamine in the caudate nucleus of rats treated with a neurotoxic regimen of MA as compared to vehicle-treated animals. The se data indicate that MA-induced neurotoxicity results in abnormal dopamine -mediated behaviors, as well as a brain region-specific impairment in stimu lated dopamine release.