PT  - JOURNAL ARTICLE
AU  - Wayne A. Cass
TI  - Decreases in Evoked Overflow of Dopamine in Rat Striatum after Neurotoxic Doses of Methamphetamine
DP  - 1997 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 105--113
VI  - 280
IP  - 1
4099  - http://jpet.aspetjournals.org/content/280/1/105.short
4100  - http://jpet.aspetjournals.org/content/280/1/105.full
SO  - J Pharmacol Exp Ther1997 Jan 01; 280
AB  - The repeated administration of methamphetamine (METH) can result in long-lasting decreases in dopamine (DA) levels, tyrosine hydroxylase activity and DA uptake sites in the striatum. However, whether these changes lead to functional alterations in the dynamics of DA release and uptake has not been extensively examined. The present study usedin vivo electrochemistry and microdialysis to examine potassium- and amphetamine-evoked release of DA in the striatum and nucleus accumbens (NAc) of METH-treated rats. Male Fischer-344 rats were administered METH (5 mg/kg s.c.) or saline four times in 1 day, at 2-hr intervals. One week later the animals were anesthetized with urethane and prepared for in vivo electrochemical recordings. The METH treatment resulted in dramatic decreases in potassium-evoked release of DA and in the rate of DA clearance in the striatum, whereas the NAc was not significantly affected. In vivo microdialysis studies demonstrated significant decreases in basal DA levels and in potassium- and amphetamine-evoked overflow of DA in the striatum of METH-treated animals. Basal and evoked DA levels in the NAc were not altered. Post-mortem levels of tissue DA were decreased by 41 to 67% in the striatum and 25 to 31% in the NAc. These results indicate that the striatum is more sensitive than the NAc to the neurotoxic effects of METH, both in measures of functional dynamics of DA signaling and in tissue levels of DA. It remains to be determined whether these functional changes in DA release and uptake are permanent or tend to recover over time. The American Society for Pharmacology and Experimental Therapeutics