ANXIOLYTIC TREATMENTS--NEUROPHARMACOLOGICAL MECHANISMS

抗焦虑治疗——神经药理学机制

• 批准号: 6243111
• 负责人: RANDALL L COMMISSARIS
• 金额: $ 6.73万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 1999-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6243111
• 关键词: amygdala; antidepressants; anxiety disorders; barbiturates; behavior test; benzodiazepines; buspirone; clonidine; conditioning; disease /disorder model; dorsal raphe nucleus; drug administration rate /duration; electrophysiology; experimental brain lesion; laboratory rat; locus coeruleus; minority institution research support; neuroanatomy; neurochemistry; neuropharmacology; neurotoxins; norepinephrine; psychopharmacology; serotonin; tranquilizer

DESCRIPTION (Adapted from the Applicant's Abstract): Based upon work conducted by the investigator and in other laboratories, there are four distinct clinically effective anxiolytic treatments that exert robust anticonflict effects in rodent models for anxiety: (1) acute benzodiazepine or barbiturate treatment, (2) chronic buspirone treatment, (3) chronic antidepressant treatment and (4) chronic clonidine treatment. The present studies are designed to examine the behavioral, neuroanatomical, and neurotransmitter mechanism for these diverse anxiolytic treatments. Studies in Specific Aim 1 are designed to examine the behavioral mechanisms for these anxiolytic treatment effects. First, the effects of these anxiolytic treatments will be determined (in some instances, re-determined) in the elevated plus maze conflict task, a non-shock conflict task which has been extensively validated as an animal model for anxiety. Second, shock sensitivity testing following the various anxiolytic treatments will be conducted to confirm that the anticonflict effects observed in the conditioned suppression of drinking (CSD) procedure are not secondary to antinociceptive effects. Studies in Specific Aim 2 will determine the importance of two limbic postsynaptic sites (central nucleus of the amygdala (CNA) and lateral septum (LS)) for the expression of the various anxiolytic treatment effects. In these studies, the effects of these anxiolytic treatments will be determined following electrolytic lesions of either the CNA, LS, or both structures. Studies in Specific Aim 3 will determine the importance of the monoamine neurotransmitters norepinephrine (NE) and 5-hydroxytryptamine (5-HT) for the expression of the anticonflict effects of the various treatments. In these studies, the effects of the anxiolytic treatments will be determined following chemical (6-OHDA, 5,7-DHT) or electrolytic lesions of NE-containing neurons in the locus ceruleus (LC), 5-HT-containing neurons within the dorsal raphe nucleus (DRN), or neurons in both sites. Studies in Specific Aim 4 will determine how these anxiolytic treatments affect the discharge rate, pattern, and drug sensitivity of single LC-NE or DRN-5-HT neurons. These studies will use standard electrophysiological recording procedures in anesthetized rats which have received the various anxiolytic treatments. Together, the proposed studies will begin to address both presynaptic and postsynaptic mechanism underlying the expression of a diverse group of anxiolytic treatments.

描述（改编自申请人的摘要）：基于工作 由研究者和其他实验室进行，有四个 不同的临床有效的抗焦虑治疗， 在啮齿动物焦虑模型中的抗冲突作用：（1）急性 苯二氮卓类或巴比妥类药物治疗，（2）慢性丁螺环酮治疗， (3)慢性抗抑郁治疗和（4）慢性可乐定治疗。 目前的研究旨在检查行为， 神经解剖学和神经递质机制， 抗焦虑治疗 具体目标1中的研究旨在检查 这些抗焦虑治疗效果的行为机制。 第一、 将确定这些抗焦虑治疗的效果（在一些实施方案中 在高架加迷宫冲突任务中， 非休克冲突任务，已被广泛验证为动物 焦虑的模型 其次，冲击敏感性测试遵循各种 将进行抗焦虑治疗，以确认抗冲突 在条件性饮酒抑制（CSD）程序中观察到的效应 并不继发于抗伤害作用。 研究具体目标2 将决定两个边缘突触后位点（中央 杏仁核（CNA）和外侧隔（LS））的表达 各种抗焦虑药物的疗效。 在这些研究中， 这些抗焦虑治疗将确定以下电解 CNA、LS或两种结构的病变。 特定目标研究 3将决定单胺类神经递质的重要性 去甲肾上腺素（NE）和5-羟色胺（5-HT）的表达 各种治疗方法的抗冲突效果。 在这些研究中， 抗焦虑治疗的效果将在以下化学治疗之后确定： （6-OHDA，5，7-DHT）或电解损伤NE神经元在 蓝斑（LC），中缝背核内含5-HT的神经元 核（DRN）或两个部位的神经元。 具体目标4将 确定这些抗焦虑治疗如何影响出院率， 单个LC-NE或DRN-5-HT神经元的模式和药物敏感性。 这些 研究将使用标准的电生理记录程序， 接受各种抗焦虑治疗的麻醉大鼠。 总之，拟议的研究将开始解决突触前和 突触后机制的表达的一组不同的 抗焦虑治疗