ONTOGENY OF METHAMPHETAMINE-INDUCED NEUROTOXICITY AND ASSOCIATED HYPERTHERMIC RESPONSE

Methamphetamine (MA) administration to adult rats results in neurotoxi city characterized by depletion of caudate-putamen (CP) dopamine (DA) and serotonin (5-HT) and an accompanying increase in glial fibrillary acidic protein (GFAP) content. The severity of MA-induced neurotoxicit y correlates with the accompanying thermoregulatory response, i.e., a hyperthermic response facilitates neurotoxicity while a hypothermic re sponse is neuroprotective. In the following study, the thermoregulator y and neurotoxic effects of MA administration (4 X 10 mg/kg) were inve stigated in developing rats at postnatal days (PND) 20, 40 and 60. Rat s at PND 20 and PND 40 were administered MA at ambient temperatures of 22 degrees C and 30 degrees C; and PND 60 rats were administered MA a t 22 degrees C only. Temperatures were measured and thermal responses were compared by calculating the total thermal response (TTR) induced by MA treatment. MA administration to PND 60 rats at 22 degrees C indu ced a hyperthermic response, resulted in a 47% reduction of neostriata l DA and a 49% increase of GFAP content. Administration of MA to PND 4 0 rats at 22 degrees C failed to induce a hyperthermic response and di d not result in reduced DA or increased GFAP. However, administration of MA to PND 40 rats at 30 degrees C induced hyperthermia, reduced neo striatal DA by 54% and increased GFAP by 70%. MA administration to PND 20 rats at either 22 degrees C or 30 degrees C did not result in DA d epletion or increased GFAP, even though MA administration to PND 20 ra ts at 30 degrees C induced hyperthermia. These results demonstrate tha t the induction of hyperthermia is necessary to exhibit MA-induced neu rotoxicity at PND 40; however, PND 20 rats are resistant to the DA dep leting effects of MA despite the induction of hyperthermia. (C) 1997 E lsevier Science B.V.