Elsevier

Brain Research

Volume 564, Issue 2, 15 November 1991, Pages 256-260
Brain Research

Multiple methamphetamine injections induce marked increases in extracellular striatal dopamine which correlate with subsequent neurotoxicity

https://doi.org/10.1016/0006-8993(91)91461-9Get rights and content

Abstract

Acutely, methamphetamine (m-AMPH) is known to stimulate a net efflux of dopamine (DA) in the striatum while inhibiting DA uptake, thus producing high extracellular concentrations of DA. Repeated administration of m-AMPH has been shown to damage DA terminals in the striatum. However, little direct information exists about the relationship between m-AMPH-induced DA overflow and neurotoxicity. In the present study, we used in vivo microdialysis to explore this topic. Four, but not 3, injections of m-AMPH (4 mg/kg, sc, at 2 h intervals) damaged striatal DA terminals as measured by a 43–51% decrease in post mortem striatal DA content 1 week later. Striatal microdialysis in awake animals during the course of m-AMPH treatment showed that DA overflow increased after each m-AMPH injection, but that approximately 1.5 h after the fourth m-AMPH injection, a striking increase in DA overflow occurred that was significantly larger than that seen after any of the previous 3 injections. Additionally, in animals receiving 4 injections of m-AMPH, cumulative DA overflow was negatively correlated with striatal DA content 1 week later (r = −0.74, P < 0.05), suggesting that the substantial DA overflow seen after the fourth m-AMPH injection is especially important in m-AMPH neurotoxicity.

References (32)

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