Methamphetamine neurotoxicity: dissociation of striatal dopamine terminal damage from parietal cortical cell body injury

Synapse. 1998 Dec;30(4):433-45. doi: 10.1002/(SICI)1098-2396(199812)30:4<433::AID-SYN10>3.0.CO;2-O.


Methamphetamine (m-AMPH) administration injures both striatal dopaminergic terminals and certain nonmonoaminergic cortical neurons. Fluoro-Jade histochemistry was used to label cortical cells injured by m-AMPH in order to identify factors that contribute to the cortical cell body damage. Rats given four injections of m-AMPH (4 mg/kg) at 2-h intervals showed hyperthermia (mean = 40.0 +/- 0.10 degrees C) and increased behavioral activation relative to animals given saline (SAL). Three days later, m-AMPH-treated animals showed indices of injury to striatal DA terminals (depletion of tyrosine hydroxylase immunoreactivity) and parietal cortical cell bodies (appearance of Fluoro-Jade stained cells). Pretreatment with a dopamine (DA) D1, D2, or N-methyl-D-aspartate (NMDA) receptor antagonist, or administration of m-AMPH in a 4 degrees C environment, prevented or attenuated m-AMPH-induced hyperthermia, behavioral activation, and injury to striatal DA terminals and parietal cortical cell bodies. Animals pretreated with a DA transport inhibitor prior to m-AMPH showed hyperthermia, behavioral activation, and parietal cortical cell body injury, but they did not show striatal DA terminal injury. Pretreatment with a 5HT transport inhibitor failed to prevent m-AMPH-induced damage to striatal DA terminals or parietal cortical cell bodies. Animals given four injections of SAL in a 37 degrees C environment became hyperthermic, but showed no injury to striatal DA terminals or cortical cell bodies. The ability of the DA transport inhibitor to block m-AMPH-induced striatal DA damage, but not cortical injury, and the inability of hyperthermia alone to cause the cortical cell body injury suggests that m-AMPH-induced behavioral activation and hyperthermia may both be necessary for the subsequent parietal cortical cell body damage.

Publication types

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

MeSH terms

  • Animals
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Corpus Striatum / pathology*
  • Dizocilpine Maleate / pharmacology
  • Dopamine / metabolism
  • Dopamine Antagonists / pharmacology
  • Dopamine Uptake Inhibitors / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Male
  • Methamphetamine / poisoning*
  • Nerve Endings / drug effects
  • Neurons / pathology
  • Neurotoxins / pharmacology*
  • Parietal Lobe / drug effects*
  • Parietal Lobe / pathology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Serotonin Uptake Inhibitors / pharmacology
  • Temperature


  • Dopamine Antagonists
  • Dopamine Uptake Inhibitors
  • Excitatory Amino Acid Antagonists
  • Neurotoxins
  • Receptors, N-Methyl-D-Aspartate
  • Serotonin Uptake Inhibitors
  • Methamphetamine
  • Dizocilpine Maleate
  • Dopamine