A SINGLE-DOSE MODEL OF METHAMPHETAMINE-INDUCED NEUROTOXICITY IN RATS - EFFECTS ON NEOSTRIATAL MONOAMINES AND GLIAL FIBRILLARY ACIDIC PROTEIN

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 monitore d for 9 h in a room with an ambient temperature of 22.0 +/- 0.5 degree s C. MA induced significant dose-dependent hyperthermia, however, no s ignificant increase in mortality occurred. Neostriatal DA, 5-HT, TH, a nd GFAP were assayed 3 days following treatment. MA induced dose-depen dent reductions of DA, 5-HT and TH, and increased GFAP. For DA, at dos es of 20, 30, or 40 mg/kg the reductions were to 71%, 49%, and 29%, an d 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 b lots 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 chang es in TH or GFAP were seen at the 10 mg/kg MA dose. These results demo nstrate that a single-dose of MA can be as effective as the widely use d four-dose every 2 h regimen, Moreover, mortality can be minimized by monitoring core body temperature and preventing MA-induced hypertherm ia from exceeding 41.5 degrees C. (C) 1998 Elsevier Science B.V. All r ights reserved.