Carnosine prevents methamphetamine-induced gliosis but not dopamine terminal loss in rats.

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 [3H]1-(2-[diphenylmethoxy]ethyl)-4-[3-phenylpropyl]piperazine([3H]GBR 12935) binding) but prevented microgliosis (increase in [3H]1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide ([3H]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 [3H]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.