NEUROPHARMACOLOGY OF NEUROENDOCRINE AND NEUROTRANSMITTER REGULATORY MECHANISMS

神经内分泌和神经递质调节机制的神经药理学

• 批准号: 3759353
• 负责人: D L MURPHY
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3759353
• 关键词: antidepressants; bulimia nervosa; buspirone; central neural pathway /tract; complementary DNA; fluoxetine; hormone regulation /control mechanism; human genetic material tag; human subject; methylphenyltetrahydropyridine; migraine; neuroendocrine system; neuropharmacology; neurotoxins; neurotransmitter transport; neurotransmitters; norepinephrine; nucleic acid sequence; piperazines; prolactin; psychophysiology; serotonin; serotonin inhibitor; serotonin receptor; transport proteins; antidepressants; bulimia nervosa; buspirone; central neural pathway /tract; complementary DNA; fluoxetine; hormone regulation /control mechanism; human genetic material tag; human subject; methylphenyltetrahydropyridine; migraine; neuroendocrine system; neuropharmacology; neurotoxins; neurotransmitter transport; neurotransmitters; norepinephrine; nucleic acid sequence; piperazines; prolactin; psychophysiology; serotonin; serotonin inhibitor; serotonin receptor; transport proteins

This project has continued to focus on investigations of the functional status of the serotonin (5-HT) neurotransmitter system in humans using 5-HT-selective agonists (e.g., m-chlorophenylpiperazine (m-CPP)) and antagonists (e.g., metergoline, ondansetron) as pharmacologic probes. In collaborative studies, Dr. E. M. Jacobsen found behavioral and neuroendocrine response differences to m-CPP administration between patients with seasonal affective disorder and matched control subjects. Many of these response differences were no longer present when the patients and controls were re-challenged with m_CPP following treatment- induced remission of their depressive symptoms. In laboratory studies related to serotonin, Dr. K.-Peter Lesch successfully isolated and sequenced a cDNA encoding the human brain vesicular monoamine transporter (VMT). Although the human VMT is highly homologous (greater than 90%) with the rat brain VMT, an extensive sequence divergence was found in one region, a large lumenal loop located between the first two transmembrane domains. A structurally identical VMT was found to be expressed in human platelets. Dr. Lesch also found that human platelets express a cell membrane serotonin transporter that is identical to the transporter found in human brain. In other studies, Dr. A.M. Andrews found that the prolonged (up to 6 months in duration) depletion of brain serotonin produced by the novel analogue of the parkinsonism-producing dopamine neurotoxin, MPTP, 2'amino-MPTP, could be prevented by pretreatment with fluoxetine or clorgyline.

该项目继续专注于对功能的调查 使用人类中5-羟色胺（5-HT）神经递质系统的状态 5-HT选择性激动剂（例如M-氯苯基哌嗪（M-CPP））和 拮抗剂（例如，恩迪尔元素，ondansetron）作为药理探针。 在协作研究中，E。M。Jacobsen博士发现了行为和 神经内分泌反应差异对M-CPP给药的差异 患有季节性情感障碍和匹配对照受试者的患者。 当这些响应差异中的许多不再存在 治疗后，患者和对照组对M_CPP重新挑战 诱导其抑郁症状缓解。 在实验室研究中 与5-羟色胺有关，K。-Peter Lesch博士成功隔离了， 测序编码人脑囊泡单胺转运蛋白的cDNA （VMT）。尽管人VMT高度同源（大于90％） 使用大鼠脑VMT，在一个中发现了广泛的序列差异 区域，一个位于前两个跨膜之间的大型腔环路 域。发现在结构上相同的VMT在人类中表达 血小板。 莱斯博士还发现人血小板表达一个细胞 膜5-羟色胺转运蛋白与发现的转运蛋白相同 在人脑中。 在其他研究中，A.M。博士安德鲁斯发现 长时间（长达6个月的持续时间）脑5-羟色胺的耗竭 由帕金森主义产生多巴胺的小说类似物制作 神经毒素，MPTP，2'amino-mptp可以通过预处理 氟西汀或神经线。