Attenuation of Methamphetamine-induced Nigrostriatal Dopaminergic Neurotoxicity in Mice by Lipopolysaccharide Pretreatment

Yin Chiu Lin；Yu-Min Kuo；Pao-Chi Liao；Chianfang G. Cherng；Su-Wen Su；Lung Yu

neurotoxicity ； methamphetamine ； dopamine ； striatum

The Chinese Journal of Physiology

50卷2期（2007 / 04 / 01）

51 - 56

英文

Immunological activation has been proposed to play a role in methamphetamine-induced dopaminergic terminal damage. In this study, we examined the roles of lipopolysaccharide, a proinflammatory and inflammatory factor, treatment in modulating the methamphetamine-induced nigrostriatal dopamine neurotoxicity. Lipopolysaccharide pretreatment did not affect the basal body temperature or methamphetamine-elicited hyperthermia three days later. Such systemic lipopolysaccharide treatment mitigated methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions in a dose-dependent manner. As the most potent dose (1 mg/kg) of lipopolysaccharide was administered two weeks, one day before or after the methamphetamine dosing regimen, methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions remained unaltered. Moreover, systemic lipopolysaccharide pretreatment (1 mg/kg) attenuated local methamphetamine infusion-produced dopamine and 3,4-dihydroxyphenylacetic acid depletions in the striatum, indicating that the protective effect of lipopolysaccharide is less likely due to interrupted peripheral distribution or metabolism of methamphetamine. We concluded a critical time window for systemic lipopolysaccharide pretreatment in exerting effective protection against methamphetamineinduced nigrostriatal dopamine neurotoxicity.

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