Elsevier

Neuroscience Letters

Volume 352, Issue 1, 27 November 2003, Pages 13-16
Neuroscience Letters

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

https://doi.org/10.1016/j.neulet.2003.08.015Get rights and content

Abstract

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 ×4, i.p. with 2 h-interval) were significantly and dose-dependently attenuated by four injections of ketoprofen (2 or 5 mg/kg ×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.

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Acknowledgements

This work was supported, in part, by Grants-in-aid for Research on Pharmaceutical and Medical Safety, for Brain Science, and for Comprehensive Research on Aging and Health from the Japanese Ministry of Health, Labour and Welfare, and by Grants-in-aid for Scientific Research (C) from the Japanese Ministry of Education, Culture, Sports, Science and Technology. We would like to thank Dr Jean Lud Cadet, Molecular Neuropsychiatry Branch, NIH/NIDA/Intramural Research Program, USA for reviewing the

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