REGULATION OF BRAIN SEROTONIN RECEPTORS

大脑血清素受体的调节

基本信息

批准号：
3379040
负责人：
Milton Teitler
金额：
$ 13.73万
依托单位：
ALBANY MEDICAL COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-12-01 至 1993-11-30
项目状态：
已结题

项目摘要

Altered sensitivity of multiple brain serotonin (5HT) receptors has been hypothesized in the etiology and/or treatment of anxiety, depression, sleep disorders, sexual behaviors, and psychosis. The roles that the multiple 5HT receptor systems play in brain function are still largely unknown, as are the neuronal mechanisms through which 5HT receptors alter cellular function. To better understand the nature of the brain's 5HT receptors have been developed and will be used in conjunction with in vivo manipulations to further our understanding of the role these receptors systems play in brain function and the effects of drugs. a) Preliminary evidence for the existence of a novel brain 5HT receptor, the 5HT1D receptors, has been uncovered. Detailed radioligand binding and adenylate cyclase studies of the 5HT1D receptor will be performed in various mammalian tissues including rat and human brain. b) in order to determine the susceptibility of the 5-HT1D receptors system to sensitivity changes, 5HT transmission in rats will be altered by acute and chronic administration of serotonin neurotoxins, receptor antagonists, agonists, anxiolytics, antidepressants, and electroconvulsive shock. Alterations in the amount of 5-HT1D receptors, the interaction of the 5HT1D receptor with its associated GTP-binding protein, and the coupling between 5HT1D receptors and brain adenylate cyclase activity due to these perturbations will be monitored. c) Preliminary studies have demonstrated that 125I-DOI labels either alternatively, a unique 5HT2 receptor with high affinity for 5HT2 agonists or, alternatively, a unique 5HT2 receptor distinct from that labelled by 3H-ketanserin. In order to address this question the distribution and regulation of the 125I-DOI labelled receptors will be determined and compared with the distribution and regulation of 3H-ketanserin (an antagonist) labelled 5-HT2 receptors in multiple brain regions. d) In order to investigate the role of the brain 5HT1A receptor systems in the actions of antidepressants and novel anxiolytics the affects of these drugs on 3H-BMY 7378 (the first 5HT1A receptor antagonist radioligand), and on the associated 5HT1A receptor-mediated inhibition of adenylate cyclase activity will be monitored.

多个脑血清素（5HT）受体的敏感性改变了在焦虑的病因和/或治疗中假设抑郁症，睡眠障碍，性行为和精神病。这多个5HT受体系统在大脑功能中扮演的角色仍然是未知的，神经元的机制也是如此哪个5HT受体改变了细胞功能。更好地理解已经开发了大脑5HT受体的性质，并且将与体内操作一起使用以进一步我们对这些受体系统在大脑中起作用的作用的理解功能和药物的影响。 a）初步证据证明新型脑5HT受体的存在，5HT1D受体具有被发现。详细的放射性结合和腺苷酸环化酶 5HT1D受体的研究将在各种包括大鼠和人脑在内的哺乳动物组织。 b）为了确定5-HT1D受体系统对敏感性改变，大鼠的5HT传播将被改变 5-羟色胺神经毒素，受体的急性和慢性给药拮抗剂，激动剂，抗焦虑药，抗抑郁药和电击电击。 5-HT1D的变化受体，5HT1D受体的相互作用与其相关的GTP结合蛋白以及5HT1D之间的耦合受体和脑腺苷酸环化酶活性将监视扰动。 c）初步研究证明了125i-doi标签，或者是独特的 5HT2受体对5HT2激动剂的亲和力高或另外，独特的5HT2受体与标记的受体不同由3H-KETANSERIN。为了解决这个问题 125i-DOI标记的受体的分布和调节将可以确定并与 3H-酮塞素（拮抗剂）在多个中标记为5-HT2受体大脑区域。 d）为了研究大脑的作用抗抑郁药和新型作用中的5HT1A受体系统抗焦虑药这些药物对3H-BMY 7378的影响（第一个 5HT1A受体拮抗剂辐射仪），在相关的5HT1A上受体介导的腺苷酸环化酶活性的抑制作用将为受监控。