Functional Monoamine Deficits Induced by Amphetamines

描述(由申请人提供)： 本应用旨在评估甲基苯丙胺(METH)和3，4-亚甲基二氧基甲基苯丙胺(MDMA)对多巴胺(DA)和5-羟色胺(5-羟色胺)终末功能的急性和慢性影响，并评价DA与5-羟色胺(5-HT)神经毒性的关系。我们将首先比较冰毒和MDMA对小鼠脑片单胺末端功能的影响。然后，我们将按照重复给药的范例来评估终端功能恢复。碳纤维电极上的伏安法将用于测量脑片中DA和5-羟色胺的释放和摄取。通过使用DA和5-羟色胺转运体基因敲除小鼠系，以及选择性神经毒素苯丙氨酸和芬氟拉明，我们将评估DA是否影响5-羟色胺的神经毒性，反之亦然。这项研究将为苯丙胺衍生物对单胺系统的不同长期影响以及DA和5-羟色胺在诱导神经毒性方面的潜在相互作用提供有价值的见解。

DESCRIPTION (provided by applicant): This application proposes to assess the acute and chronic effects of methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA) on dopamine (DA) and serotonin (5-HT) terminal function and evaluate the relationship between DA and 5-HT neurotoxicity. We will first compare the effects of METH and MDMA on monoamine terminal function acutely in mouse brain slices. Then we will evaluate terminal function recovery following a repeated administration paradigm. Voltammetry at carbon fiber electrodes will be used to measure release and uptake of DA and 5-HT in brain slices. With the use of the DA and the 5-HT transporter knockout mouse lines, and the selective neurotoxins phentermine and fenfluramine, we will evaluate whether DA influences 5-HT neurotoxicity, and vice versa. The research proposed will provide valuable insights into the differential long-term impact of amphetamine derivatives on monoamine systems and the potential interactions between DA and 5-HT in inducing neurotoxicity.