REGULATION OF BRAIN SEROTONIN RECEPTORS

多个脑5-羟色胺(5-羟色胺)受体的敏感性改变 在焦虑症的病因和/或治疗中被假设， 抑郁、睡眠障碍、性行为和精神错乱。这个 多个5-羟色胺受体系统在脑功能中的作用 在很大程度上仍然是未知的，就像神经机制通过 哪种5-羟色胺受体会改变细胞功能。为了更好地理解 大脑5-羟色胺受体的本质已经被开发出来 将与体内操作结合使用，以进一步 我们对这些受体系统在大脑中所起作用的理解 药物的作用和效果。A)初步证据表明 大脑中存在一种新的5HT1D受体，即5HT1D受体 已经被发现了。详细的放射性配基结合和腺苷环化酶 5HT1D受体的研究将在不同的 哺乳动物组织，包括大鼠和人脑。B)为了 测定5-HT1D受体系统对 敏感性改变，5-羟色胺在大鼠体内的传递将被改变 5-羟色胺神经毒素受体的急慢性给药 拮抗剂、激动剂、抗焦虑药、抗抑郁剂和 电击惊厥。5-HT1D含量的变化 受体，5HT1D受体与其受体的相互作用 相关GTP结合蛋白及其与5HT1D的偶联 受体与脑腺苷环化酶活性 将对扰动进行监控。C)初步研究已 演示了125I-DOI标签或者是唯一的 与5HT2激动剂有高亲和力的5HT2受体或， 或者，一种独特的5HT2受体与标记的受体不同 由~3H-酮丝氨酸合成。为了解决这个问题， ~(125)I-DOI标记受体Will的分布和调控 被确定并与分布和调节相比较 ~3H-酮丝氨酸(一种拮抗剂)标记的5-HT2受体 大脑区域。D)为了研究大脑的作用 5HT1a受体系统在抗抑郁药中的作用及新进展 抗焦虑药物对~3H-BMY 7378细胞的影响 5HT1a受体拮抗剂放射性配基)，以及相关的5HT1a 受体介导的腺苷环化酶活性抑制将是 被监视着。

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.