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Vol. 280, Issue 1, 105-113, 1997
Department of Anatomy and Neurobiology, University of Kentucky
College of Medicine, Lexington, Kentucky
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 used
in 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.
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