title: Attenuation of methamphetamine-induced nigrostriatal dopaminergic neurotoxicity in mice by lipopolysaccharide pretreatment.
abstract: 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 pro-inflammatory 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 methamphetamine-induced nigrostriatal dopamine neurotoxicity.
authors.affiliation: Institute of Behavioral Medicine, National Cheng-Kung University College of Medicine Tainan 701, Taiwan.
authors.forename: Yin Chiu
authors.initials: YC
authors.lastname: Lin
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Kuo
authors.forename: Pao-Chi
authors.initials: PC
authors.lastname: Liao
authors.forename: Chianfang G
authors.initials: CG
authors.lastname: Cherng
authors.forename: Su-Wen
authors.initials: SW
authors.lastname: Su
authors.forename: Lung
authors.initials: L
authors.lastname: Yu
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001479:Basal Ganglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000378:metabolism / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005334:Fever / Q000378:metabolism / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000378:metabolism / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000276:immunology / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000502:physiology
chemical_list: D015259:Dopamine Agents; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; D008694:Methamphetamine; D004298:Dopamine