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

Brain Res. 1991 Nov 15;564(2):256-60. doi: 10.1016/0006-8993(91)91461-9.


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 less than 0.05), suggesting that the substantial DA overflow seen after the fourth m-AMPH injection is especially important in m-AMPH neurotoxicity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Caudate Nucleus / drug effects
  • Caudate Nucleus / metabolism
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Dialysis
  • Dopamine / metabolism*
  • Extracellular Space / drug effects
  • Extracellular Space / metabolism*
  • Male
  • Methamphetamine / administration & dosage
  • Methamphetamine / pharmacology*
  • Methamphetamine / toxicity
  • Nervous System Diseases / chemically induced*
  • Nervous System Diseases / physiopathology
  • Putamen / drug effects
  • Putamen / metabolism
  • Rats
  • Rats, Inbred Strains


  • 3,4-Dihydroxyphenylacetic Acid
  • Methamphetamine
  • Dopamine