NEUROBIOLOGY OF STIMULANT PSYCHOTOMIMETIC DRUGS

儿茶酚胺能神经元功能的改变与 精神病和情感障碍。对儿茶酚胺的认识 神经元功能可以阐明神经基础，以及提供 洞察这些严重疾病的治疗。我们的目标是学习 精神活性药物作用机制的研究进展 用单细胞记录技术研究儿茶酚胺神经元 大鼠体内的微离子电泳法。基于研究结果 在我们的实验室中，我们希望研究四个主要主题。首先，我们有 发现苯丙胺(AMP)的d-和1-异构体有区别 降低黑质(A9核)放电频率的作用 腹侧被盖区(A10核)多巴胺(DA)神经元。D-AMP有 对A9和A10神经元的作用相同；然而，1-AMP相对 对A9神经元无效，但对A10神经元相当有效。我们希望 确定为什么这些AMP异构体对这两种DA有不同的影响 原子核。第二，AMP和非AMP(如氨基甲酸)中枢兴奋剂 对多巴胺和去甲肾上腺素(NE)神经元的影响不同。我们希望 进一步研究非AMP类中枢神经系统兴奋剂对DA的作用机制 和去甲肾上腺素神经元。第三，AMP和非AMP激动剂释放和阻断DA 多巴胺轴突终末区域的摄取。我们希望研究这些药物是否 在DA细胞体/树突区域也有同样的作用。最后， 我们实验室的生化研究表明，中枢作用 肌松药(如唑沙拉明、氯唑沙宗和甲芬尼辛) 影响纹状体DA机制。我们希望确定是否和到 它们影响DA和NE脉冲流的机制是什么。

Alterations in catecholaminergic neuron function have been implicated in psychosis and affective disorders. An understanding of catecholamine neuron function may shed light on the neural basis, as well as provide insight for treatment, of these serious diseases. Our goal is to study the mechanisms of action of psychoactive drugs on catecholamine-containing neurons using single cell recording and microiontophoretic techniques in the rat. Based upon research findings in our laboratories, we wish to pursue four major topics. First, we have found that the d- and 1-isomers of amphetamine (AMP) have differential effects in reducing the firing rates of substantia nigra (nucleus A9) and ventral tegmental area (nucleus A10) dopamine (DA) neurons. d-AMP has equipotent effects on A9 and A10 neurons; however, 1-AMP is relatively impotent on A9 neurons, but is quite potent on A10 neurons. We wish to determine why these AMP isomers have differential effects on these two DA nuclei. Second, AMP and non-AMP (e.g. amfonelic acid) CNS stimulants influence DA and norepinephrine (NE) neurons differently. We wish to further study the mechanisms of action of non-AMP CNS stimulants on DA and NE neurons. Third, AMP and non-AMP stimulants release and block DA uptake at DA axon terminal regions. We wish to study whether these drugs also have the same effects at the DA cell body/dendrite region. Finally, biochemical research from our laboratories suggest that centrally acting muscle relaxants (e.g. zoxzxolamine, chlorzoxazone and mephenesin) influence striatal DA mechanisms. We wish to determine whether and by what mechanisms they influence DA and NE impulse flow.