RECEPTORS, CALCIUM AND MECHANISMS OF ECT

受体、钙和 ECT 机制

• 批准号: 3475417
• 负责人: Laura J. Fochtmann
• 金额: $ 8.61万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-08-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3475417
• 关键词: adrenergic receptor; autoradiography; brain mapping; calcium channel; calcium flux; clinical depression; disease /disorder model; dopamine receptor; electroconvulsive therapy; electrodes; learned helplessness; receptor binding; second messengers; stroke; voltage gated channel

The aim of this proposal is to address mechanisms of action for clinical EGT by localizing regions where electroconvulsive shock (ECS) induces changes in receptors, second messenger systems and ion channels. It will focus more specifically on systems in which changes have previously been seen with chronic ECS and which have calcium as a final common output and mediator. These are: alpha1 receptors with links to phosphatidylinositol system; beta and D1 receptors, with stimulatory links to the adenylate cyclase second messenger system and D2 receptors, with inhibitory links to the adenylate cyclase. Activation of the adenylate cyclase system can lead to phosphorylation of calcium ion channels, indirectly altering calcium influx into neurons. The phosphatidylinositol system leads to direct release of calcium from intracellular stores and is also capable of phosphorylating ion channels. Numbers of ion channels can be regulated as well. Therefore, the possibility that chronic ECS directly effects regulation of L-type and N-type voltage dependent calcium channels will also be examined. The principal method used to determine ECS-induced changes in binding to receptors and their effector systems will be quantitative autoradiography. The time course of these alterations will be determined as will kinetic analysis of binding. A second group of experiments will assess whether these ECS-induced changes differ with various ECS stimulus electrode placements, analogous to the unilateral and bilateral electrode placements used clinically. It will also assess effects of stimulus intensity and waveform on these alterations. Finally, the changes which ECS induces in binding to receptors, calcium channels and components of second messenger systems in these normal rats will be compared with changes induced by ECS in two animal models of depression; learned helplessness (both behaviorally and genetically induced) and cortical lesion-induced model of post stroke depression. The long term goal of these studies is to understand the mechanism of action of electroconvulsive therapy (ECT). ECT remains an effective treatment for severe depression and is especially useful in treating psychotic affective disorders. An improved understanding of its mechanism of action may, therefore, aid in the design of more effective treatments for these illnesses. It may also provide a framework for understanding the underlying pathophysiologies of depression.

本提案的目的是解决作用机制的临床