ELECTROCONVULSIVE SHOCK EFFECTS ON BRAIN RECEPTORS

电休克对脑感受器的影响

• 批准号: 3380665
• 负责人: KENNETH J KELLAR
• 金额: $ 13.92万
• 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/3380665
• 关键词: alpha adrenergic receptor; amphetamines; antidepressants; autoradiography; axon; beta adrenergic receptor; brain mapping; brain metabolism; cyclic AMP; electroconvulsive therapy; experimental brain lesion; imipramine; laboratory rat; mental disorder chemotherapy; neurochemistry; neurotransmitter receptor; 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.

本研究的总体目标是比较 电休克（ECS）给药的影响， 对肾上腺素能和去甲肾上腺素能的抗抑郁药 大鼠大脑中的受体。 特别是下列 假设将被测试：1）ECS不同于大多数 抗抑郁药物治疗对5-HT-2的影响 受体，2）ECS不同于大多数抗抑郁药 药物治疗对上调的β-肾上腺素能受体的影响 受体。 为了验证后一个假设，我们将使用一个新的 模型中，在高度特异性的5-HT损伤后 神经元或抑制5-HT合成，β-肾上腺素能 大脑中的受体明显增加。 在具体的 本研究的目的是：1）确定ECS的效果 和抗抑郁药物对增加的 β-肾上腺素能受体通过测量配体结合和 异丙肾上腺素刺激脑中环AMP产生。 2)到 使用定量放射自显影来识别和比较 β-肾上腺素能受体的特定脑区 减少ECS和抗抑郁药物，并确定 β受体亚型受这些治疗的影响。 3)到 通过定量放射自显影术识别特定区域 和大脑皮层层，其中5-HT-2受体是 抗抑郁药可使其降低。 4)到 比较ECS与抗抑郁药对5-HT-2的影响 和α-1-肾上腺素能受体介导的磷酸肌醇 水解 5)为了确定去甲肾上腺素的损伤 轴突改变ECS或抗抑郁药物对 5-HT-2受体。 这些研究应该提供有关影响的新信息 ECS和抗抑郁药物对受体系统的影响 这两种神经递质最常与 抑郁症及其治疗 这些信息应该 有助于最终理解神经化学物质 ECS和抗抑郁药物的作用，以及潜在的 电休克治疗临床效果的基本原理。