PSYCHOTOGENIC DRUG ACTION ON CHEMICALLY DEFINED NEURONS

对化学定义的神经元的致精神药物作用

• 批准号: 2243438
• 负责人: GEORGE AGHAJANIAN
• 金额: $ 27.98万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1975
• 资助国家: 美国
• 起止时间: 1975-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2243438
• 关键词: G protein; afferent nerve; albino rat; brain; central neural pathway /tract; cerebral cortex; drug tolerance; electrophysiology; hallucinogens; immunocytochemistry; indoleamine; locus coeruleus; neurons; neurotransmitters; phenylethylamines; phosphatidylinositols; protein kinase C; psychotomimetic drug; receptor coupling; second messengers; serotonin; serotonin receptor

The general purpose of this project continues to be the investigation of the electrophysiological actions of the indoleamine/phenethethylamine class of psychedelic hallucinogens on identified neurons of the rat brain. Specific aims are: 1. To investigate the pathways by which hallucinogenic drugs alter the activity and reactivity of locus coeruleus neurons in vivo: The role of major afferent inputs will be examined since the effect of psychedelic hallucinogens on locus coeruleus neurons does not appear to be due to a direct action on these cells. 2. To analyze cellular subtypes and membrane mechanisms underlying 5-HT2- receptor-mediated excitatory actions of serotonin and hallucinogenic drugs on identified neurons in brain slices. The membrane mechanisms underlying the excitatory/facilitatory effects of serotonin and hallucinogenic drugs will be studied on identified neurons in brain slices from facial nucleus and cerebral cortex. 3. To evaluate the role of G proteins and protein kinase C in modulating neuronal responses to serotonin and hallucinogenic drugs. The involvement of G proteins and protein kinase C in the mediation of 5-HT2 responses will be examined in brain slices from cerebral cortex and facial nucleus. 4. To study the cellular mechanisms of tolerance and sensitization to hallucinogenic drugs. Chronic studies will be conducted in terms of known changes in receptor and effector mechanisms (e.g., 5-HT2 receptor downregulation by hallucinogenic drugs). The value of the proposed research would be to advance knowledge about the mechanism of action of a major class of drugs, the psychedelic hallucinogens. In addition to any implications for the treatment of drug overdose (or other untoward reactions), this information could aid the rational development of more efficacious antipsychotic drugs, which, for example, might act upon convergent effector mechanisms and second messenger systems rather than the initial receptor site as is the case with currently available treatments.

该项目的一般目的继续是对 的电生理作用 吲哚胺/苯乙乙胺类迷幻致幻剂的类别 鉴定出大鼠脑的神经元。具体目的是： 1。研究致幻药改变的途径 体内基因座神经元的活性和反应性： 由于迷幻的影响，将检查主要传入的投入 基因座神经元上的致olcogengengengengengengengengengengengles似乎并不是由于 直接对这些细胞作用。 2。分析5-HT2-基础的细胞亚型和膜机制 血清素和致幻药的受体介导的兴奋作用 在脑切片中鉴定出的神经元上。膜机制 5-羟色胺和致幻药的兴奋性/促进作用 将研究面部核的脑切片中鉴定的神经元 和大脑皮层。 3。评估G蛋白和蛋白激酶C在调节中的作用 神经元对5-羟色胺和致幻药的反应。参与 5-HT2反应中的G蛋白和蛋白激酶C将 在大脑皮层和面部核中进行大脑切片中的检查。 4。研究耐受性和敏化的细胞机制 致幻药。慢性研究将以已知 受体和效应器机制的变化（例如5-HT2受体 致幻药的下调）。 拟议的研究的价值将是提高有关 一类主要药物的作用机理，迷幻药 致幻剂。除了对药物治疗的任何影响 用药过量（或其他不良反应），此信息可以帮助 更有效的抗精神病药的合理发展，这是 例如，可能采取趋同效应器机制和第二使者的作用 系统而不是当前的初始受体站点 可用的治疗。