ELECTROCONVULSIVE SHOCK EFFECTS ON BRAIN RECEPTORS

电休克对脑感受器的影响

• 批准号: 3380663
• 负责人: KENNETH J KELLAR
• 金额: $ 12.8万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3380663
• 关键词: amphetamines; antidepressants; autoradiography; axon; brain mapping; brain metabolism; cyclic AMP; electroconvulsive therapy; experimental brain lesion; imipramine; mental disorder chemotherapy; neurochemistry; norepinephrine; p chlorophenylalanine; phenelzine; phosphatidylinositols; radiotracer; serotonin

The overall objectives of this research are to compare the effects of administration of electroconvulsive shock (ECS) and antidepressant drugs on serotonergic and noradrenergic receptors in rat brain. In particular, the following hypotheses will be tested: 1) that ECS differs from most antidepressant drug treatments in its effects on 5-HT-2 receptors, and 2) that ECS differs from most antidepressant drug treatments in its effects on up-regulated beta-adrenergic receptors. To test the latter hypothesis, we will use a new model in which following highly specific lesions of 5-HT neurons or inhibition of 5-HT synthesis, beta-adrenergic receptors are markedly increased in brain. Among the specific aims of this research are: 1) To determine the effects of ECS and antidepressant drugs on the increased number of beta-adrenergic receptors by measuring ligand binding and isoproterenol-stimulated cyclic AMP production in brain. 2) To use quantitative autoradiography to identify and compare the specific brain regions in which beta-adrenergic receptors are decreased by ECS and antidepressant drugs, and to identify the beta receptor subtype affected by these treatments. 3) To identify by quantitative autoradiography the specific regions and layers of cerebral cortex in which 5-HT-2 receptors are increased by ECS and decreased by antidepressant drugs. 4) To compare the effects of ECS and antidepressant drugs on 5-HT-2 and alpha-1-adrenergic receptor-mediated phosphoinositide hydrolysis. 5) To determine whether lesions of norepinephrine axons alter the effects of ECS or antidepressant drugs on 5-HT-2 receptors. These studies should provide new information about the effects of ECS and antidepressant drugs on the receptor systems for the two neurotransmitters that have been most often implicated in depression and its treatment. This information should contribute to an eventual understanding of the neurochemical effects of ECS and antidepressant drugs and potentially to the rationale for the clinical effects of electroconvulsive therapy.

这项研究的总体目标是比较 电惊厥性休克(ECS)给药的效果 抗抑郁药物对5-羟色胺能和去甲肾上腺素能的影响 大鼠大脑中的受体。特别是，以下内容 将检验假设：1)ECS与MOST不同 抗抑郁药物治疗对5-羟色胺-2的影响 受体，以及2)ECS与大多数抗抑郁药不同 药物治疗对上调β-肾上腺素能的影响 感受器。为了检验后一种假设，我们将使用一个新的 5-羟色胺高度特异性损伤后的模型 神经元或抑制5-羟色胺合成，β-肾上腺素能 大脑中的受体显著增加。在具体的 本研究的目的是：1)确定ECS的效果 而抗抑郁药物的数量增加了 通过测定配基结合和β-肾上腺素能受体 异丙肾上腺素刺激脑内环磷酸腺苷的产生。2)至 使用定量放射自显影来识别和比较 β-肾上腺素能受体所在的特定脑区 被ECS和抗抑郁药物降低，并确定 β受体亚型受这些处理的影响。3)至 用定量放射自显影识别特定区域 以及大脑皮层中5-羟色胺-2受体的层 ECS升高，抗抑郁药降低。4)至 体外循环与抗抑郁药对5-羟色胺-2的影响比较 和α-1-肾上腺素能受体介导的肌醇磷脂 水解液。5)确定去甲肾上腺素的损害是否 轴突改变ECS或抗抑郁药物对 5-HT-2受体。 这些研究应该会提供有关影响的新信息。 ECS和抗抑郁药物在受体系统上的作用 两种神经递质最常被牵连到 抑郁症及其治疗。此信息应为 有助于对神经化学物质的最终理解 ECS和抗抑郁药物的影响以及对潜在的 电休克治疗临床效果的理论基础。