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 神经元功能可能揭示神经基础，以及提供 对这些严重疾病的治疗有深刻的见解。 我们的目标是学习 精神活性药物的作用机制 使用单细胞记录的含儿茶酚胺神经元， 大鼠微离子电渗技术。 根据研究结果， 在我们的实验室里，我们希望研究四个主要课题。 首先我们得 发现苯丙胺（AMP）的d-和1-异构体具有差异 降低黑质（核A9）放电率的作用， 腹侧被盖区（A10核）多巴胺（DA）神经元。 d-AMP具有 对A9和A10神经元的等效作用;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（例如氨醛酸）CNS兴奋剂 对DA和NE神经元的影响不同。 我们希望 进一步研究非AMP CNS兴奋剂对DA的作用机制 和NE神经元。 第三，AMP和非AMP兴奋剂释放和阻断DA 在DA轴突末端区域的摄取。 我们希望研究这些药物 在DA单元体/枝晶区域也具有相同的效果。 最后， 我们实验室的生化研究表明， 肌肉松弛剂（如唑沙丁胺、氯唑沙宗和美芬甘油醚） 影响纹状体DA机制。 我们希望确定， 它们影响DA和NE冲动流的机制。

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.