RT Journal Article
SR Electronic
T1 Methamphetamine-Induced Neurotoxicity Alters Locomotor Activity, Stereotypic Behavior, and Stimulated Dopamine Release in the Rat
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 9141
OP 9148
DO 10.1523/JNEUROSCI.19-20-09141.1999
VO 19
IS 20
A1 Tanya L. Wallace
A1 Gary A. Gudelsky
A1 Charles V. Vorhees
YR 1999
UL http://www.jneurosci.org/content/19/20/9141.abstract
AB The neurochemical evidence of methamphetamine (MA)-induced toxicity to dopaminergic nerve terminals is well documented; however, the functional consequences are not clearly defined. The present study was designed to investigate whether MA-induced dopamine depletions affect locomotor activity, stereotypic behavior, and/or extracellular dopamine concentrations in the neostriatum. 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 effects 1 week later. Animals that had received the neurotoxic regimen of MA showed a reduction in both caudate nucleus and nucleus accumbens dopamine contents 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 vehicle-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 augmented stereotypic response and a significantly attenuated increase in the extracellular concentration of dopamine in the caudate nucleus of rats treated with a neurotoxic regimen of MA as compared to vehicle-treated animals. These data indicate that MA-induced neurotoxicity results in abnormal dopamine-mediated behaviors, as well as a brain region-specific impairment in stimulated dopamine release.