Methamphetamine-induced neurotoxicity in mouse brain is attenuated by ketoprofen, a non-steroidal anti-inflammatory drug

We examined effects of non-steroidal anti-inflammatory drugs (NSAIDs) on methamphetamine (METH)-induced neurotoxicity. Marked reduction of dopamine transporter-positive signals and accumulation of microglial cells in the striatum after METH injections (4 mg/kg x 4, i.p. with 2 h-interval) were significantly and dose-dependently attenuated by four injections of ketoprofen (2 or 5 mg/kg X 4, s.c.) given 30 min prior to each METH injection, but not by either a low or high dose of aspirin. The present results suggest that the protective effects of ketoprofen against METH-induced neurotoxicity and microgliosis might be based on its inhibitory activity on inflammatory response or on microglia activation, but not on its cyclooxygenase-inhibiting property. This provides a possible new strategy against METH-induced neurotoxicity using commonly used NSAIDs. (C) 2003 Elsevier Ireland Ltd. All rights reserved.