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 x4, i.p. with 2 h-interval) were significantly and dose-dependently attenuated by four injections of ketoprofen (2 or 5 mg/kg x4, 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.
Asanuma
Masato
M
Department of Brain Science, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikatacho, Okayama 700-8558, Japan. asachan@cc.okayama-u.ac.jp
Tsuji
Takeshi
T
Miyazaki
Ikuko
I
Miyoshi
Ko
K
Ogawa
Norio
N
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D007660:Ketoprofen / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000187:drug effects / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008694:Methamphetamine; D007660:Ketoprofen