A single dose model of methamphetamine-induced neurotoxicity in rats: effects on neostriatal monoamines and glial fibrillary acidic protein

Brain Res. 1998 Sep 21;806(1):1-7. doi: 10.1016/s0006-8993(98)00656-8.


The neurotoxic effects of a single administration of methamphetamine (MA) were studied under conditions conducive to MA-induced hyperthermia. After a single dose of MA (10, 20, 30, or 40 mg/kg, s. c.) or saline (3 ml/kg) to Sprague-Dawley CD rats, rectal temperatures were monitored for 9 h in a room with an ambient temperature of 22.0+/-0.5 degrees C. MA induced significant dose-dependent hyperthermia, however, no significant increase in mortality occurred. Neostriatal DA, 5-HT, TH, and GFAP were assayed 3 days following treatment. MA induced dose-dependent reductions of DA, 5-HT and TH, and increased GFAP. For DA, at doses of 20, 30, or 40 mg/kg the reductions were to 71%, 49%, and 29%, and for 5-HT were to 73%, 44%, and 19% of control values. No reductions were seen after the 10 mg/kg dose. Semiquantitative analysis Western blots of TH and GFAP demonstrated that TH was reduced to 52%, 75%, and 28%, and GFAP was increased to 125%, 134%, and 149% of control values at MA doses of 20, 30, or 40 mg/kg, respectively. No significant changes in TH or GFAP were seen at the 10 mg/kg MA dose. These results demonstrate that a single-dose of MA can be as effective as the widely used four-dose every 2 h regimen. Moreover, mortality can be minimized by monitoring core body temperature and preventing MA-induced hyperthermia from exceeding 41.5 degrees C.

Publication types

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

MeSH terms

  • Animals
  • Biogenic Monoamines / metabolism*
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism
  • Fever / chemically induced
  • Glial Fibrillary Acidic Protein / metabolism*
  • Male
  • Methamphetamine / administration & dosage*
  • Methamphetamine / poisoning
  • Neurotoxins / administration & dosage*
  • Neurotoxins / poisoning
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism
  • Tyrosine 3-Monooxygenase / metabolism


  • Biogenic Monoamines
  • Glial Fibrillary Acidic Protein
  • Neurotoxins
  • Serotonin
  • Methamphetamine
  • Tyrosine 3-Monooxygenase
  • Dopamine