EFFECTS OF NEUROTOXIC DOSES OF METHAMPHETAMINE ON POTASSIUM AND AMPHETAMINE EVOKED OVERFLOW OF DOPAMINE IN THE STRIATUM OF AWAKE RATS

The effects of neurotoxic doses of methamphetamine on basal and evoked overflow of dopamine in the striatum were examined in awake rats usin g microdialysis. Male Fischer-344 rats were administered methamphetami ne (5 mg/kg s.c.) or saline four times in 1 day at 2-h intervals. Micr odialysis experiments were carried out 1 week later. Basal levels of d opamine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid were re duced in the striatum of the methamphetamine-treated animals. Local ap plication of excess potassium (100 mM) and amphetamine (100 mu M), and intraperitoneal injection of amphetamine (1.5 mg/kg), led to increase d levels of extracellular dopamine in the striatum of both methampheta mine- and saline-treated rats. However, the increase was significantly less in the methamphetamine-treated animals. Tissue levels of dopamin e and metabolites were reduced in the striata of rats treated with met hamphetamine. These results indicate that treatment with neurotoxic do ses of methamphetamine can lead to functional changes in dopamine rele ase in the striatum of Fischer-344 rats. (C) 1998 Published by Elsevie r Science Ireland Ltd. Ail rights reserved.