Abstract

The neuroprotective effect of carnosine, an endogenous antioxidant, was examined against methamphetamine-induced neurotoxicity in rats. Carnosine pretreatment had no effect on dopamine terminal loss induced by methamphetamine (assessed by [H-3]1-(2-[diphenylmethoxy]ethyl)-4-[3-phenylpropyl]piperazine([H-3]GBR 12935) binding) but prevented microgliosis (increase in [H-3]1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide ([H-3]PK 11195) binding) in striatum. The 27-kDa heat-shock protein (HSP27) expression was used as indicator of astroglial stress. Methamphetamine treatment induced the expression of HSP27 in striatum and hippocampus, which was inhibited by carnosine, indicating a protective effect. Carnosine had no effect on methamphetamine-induced hyperthermia. Thus, carnosine prevents the microgliosis in striatum (where we did not detect loss of serotonergic terminals by [H-3]paroxetine binding) and the expression of HSP27 in all the areas, but fails to prevent methamphetamine-induced loss of dopamine reuptake sites. Therefore, carnosine inhibits only some of the consequences of methamphetamine neurotoxicity, where reactive oxygen species play an important role. (C) 2002 Elsevier Science B.V. All rights reserved.