Fornai F, Bassi L, Torracca M T, Scalori V, Corsini G U
Institute of Pharmacology, School of Medicine, University of Pisa, Italy.
Eur J Pharmacol. 1995 Sep 5;283(1-3):99-102. doi: 10.1016/0014-2999(95)00313-a.
Evidence is accumulating that norepinephrine depletion enhances the neurotoxic effect of the parkinsonism inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this study we investigated whether norepinephrine loss potentiates methamphetamine-induced striatal dopamine depletion. Injection of C57BL/6N mice with methamphetamine (2 x 5 mg/kg i.p., at 2-h intervals) produced only a partial (50%) striatal dopamine depletion 7 days after drug administration. Pretreatment with the selective noradrenergic neurotoxin N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4; 50 mg/kg i.p.) enhanced methamphetamine-induced striatal dopamine depletion by 86%, without decreasing striatal dopamine levels when injected alone. Our results extend previous findings obtained with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine in DSP-4-pretreated mice.
越来越多的证据表明，去甲肾上腺素耗竭会增强帕金森病诱导性神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）的神经毒性作用。在本研究中，我们调查了去甲肾上腺素缺失是否会增强甲基苯丙胺诱导的纹状体多巴胺耗竭。给C57BL/6N小鼠注射甲基苯丙胺（2×5mg/kg腹腔注射，间隔2小时），在给药7天后仅导致纹状体多巴胺部分（50%）耗竭。用选择性去甲肾上腺素能神经毒素N-（-2-氯乙基）-N-乙基-2-溴苄胺（DSP-4；50mg/kg腹腔注射）预处理，可使甲基苯丙胺诱导的纹状体多巴胺耗竭增加86%，单独注射时不会降低纹状体多巴胺水平。我们的结果扩展了先前在DSP-4预处理小鼠中使用多巴胺能神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶获得的发现。
