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

《The Chinese Journal of Physiology》 50卷2期 (2007/04) Pp. 51-56

並列摘要

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.

並列關鍵字

neurotoxicity ； methamphetamine ； dopamine ； striatum

參考文獻

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