ENHANCEMENT OF COCAINE-INDUCED HYPERTHERMIA FAILS TO ELICIT NEUROTOXICITY

The neurotoxic potential of cocaine when administered under conditions conducive to the initiation of hyperthermia was investigated. Rats we re administered cocaine at ambient temperatures of 22 degrees C or 30 degrees C. To determine the thermal response, body temperatures were m easured every 30 min and the total thermal response (TTR), representin g the area under the temperature vs. time curve, was calculated. Salin e administered at 22 degrees C or 30 degrees C resulted in a normal th ermal response (TTR = 9.8 +/- 0.9 and 11.2 +/- 0.9, respectively). Coc aine administration resulted in ambient temperature-dependent hyperthe rmia. Cocaine (4 x 25 mg/kg) administered at 22 degrees C resulted in a TTR of 15.1 +/- 0.9 whereas cocaine (4 x 15 or 25 mg/kg) administere d at 30 degrees C resulted in TTRs of 22.2 +/- 0.9 and 21.9 +/- 0.8, r espectively. Regardless of the dose or thermal response, cocaine admin istration did not result in depletion of dopamine (DA) or serotonin (5 -HT) in the caudate-putamen. Cocaine administration also failed to ind uce an increase in the concentration of glial fibrillary acidic protei n (GFAP), a marker for neurotoxicity. These results demonstrate that h yperthermia does not promote cocaine-induced neurotoxicity in the rat caudate-putamen. (C) 1998 Elsevier Science Inc.