ROLE OF DOPAMINE IN THE DEVELOPMENT OF DRUG-INDUCED NEUROTOXICITY

多巴胺可能参与多种神经毒性的研究 集中作用的药物正在接受检查。假想的角色 多巴胺与帕金森综合征诱导物的选择性毒性 1-MPTP在小鼠身上进行了研究，这些药物可以改变 内源性多巴胺以确定的方式合成。治疗方法： 酪氨酸羟化酶竞争性抑制剂，α-甲基-对酪氨酸 不改变L-MPTP的多巴胺能神经毒性 大剂量的多巴胺前体L-多巴。 在相关实验中，多巴胺需求背后的机制 中枢性刺激剂的合成及其性激素能神经毒性的研究 对甲基苯丙胺进行了研究。5-羟色胺能神经元被显示为 多巴胺通过其高亲和力摄取系统。这种领悟是 抗坏血酸的促进作用就像甲基苯丙胺的神经毒性一样 体内需要正常水平的抗坏血酸。最近，我们有了 也证明了药物刺激在体内诱导的多巴胺释放 确实进入了5-羟色胺能神经元，在那里它取代了内源性的 血清素。

The possible involvement of dopamine in the neurotoxicity of a number of centrally acting drugs is being examined. The hypothesized role of dopamine in the selective toxicity of the parkinsonism-inducing compound 1-MPTP was investigated using mice pretreated with agents which alter endogenous dopamine synthesis in a defined manner. Treatment with the competitive inhibitor of tyrosine hydroxylase, alpha-methy-p-tyrosine, did not alter the dopaminergic neurotoxicity of l-MPTP nor did treatment with large doses of the dopamine precursor L-DOPA. In related experiments, the mechanism behind the requirement for dopamine synthesis in the sesrotonergic neurotoxicity of central stimulants such as methamphetamine was studied. Serotonergic neurons were shown to take up dopamine via their high affinity uptake system. This uptake was facilitated by ascorbic acid just as the neurotoxicity of methamphetamine requires normal levels of ascorbic acid in vivo. More recently we have also demonstrated that dopamine release induced by drug stimulation in vivo does enter serotonergic neurons where it displaces endogenous stores of serotonin.