DORSAL RAPHE NUCLEUS SEROTONIN NEURONS IN ALCOHOLISM

酗酒时中缝背核血清素神经元

• 批准号: 2769206
• 负责人: MARK D UNDERWOOD
• 金额: $ 23.29万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2769206
• 关键词: alcoholism /alcohol abuse; brain mapping; clinical research; dorsal raphe nucleus; histopathology; human subject; human tissue; interview; neuropathology; neurotoxicology; neurotransmitter metabolism; neurotransmitter transport; postmortem; serotonin; serotonin inhibitor; serotonin transporter

DESCRIPTION: (Adapted from the Investigator's Abstract) Serotonin deficiency in alcoholics is hypothesized based principally on observations of reduced serotonin metabolites in the cerebrospinal fluid, the efficacy of serotonin agonists and uptake inhibitors in reducing alcohol consumption in humans and animal models and biochemical abnormalities in alcohol preferring rat strains. Preliminary postmortem evidence is presented of a loss of serotonin-synthesizing neurons in the dorsal raphe nucleus (DRN) and a decrease in the number of serotonin nerve terminals in the prefrontal cortex of alcoholics. A comprehensive postmortem study of the serotonin system is proposed to determine the changes in the serotonin system in alcoholics. To further evaluate the significance of any findings we will determine whether these changes are correlated with the duration or severity of alcohol dependence. The proposal has been extensively modified to meet the criticisms of the previous review. The brains of 20 subjects meeting DSM-IV criteria for alcohol abuse or dependence and 20 nonpsychiatric controls will be examined. Alcohol abuse/dependence will be diagnosed by psychological autopsy. Computer-assisted stereology and morphometry of DRN serotonin neurons labeled with antiphenylalanine hydroxylase antibodies in alcoholics and non-psychiatric controls will determine: the number, density, distribution and morphology of DRN serotonergic neurons as measures of neurodegeneration. In the ventrolateral prefrontal cortex, primary motor cortex and visual cortex, measurement of serotonin transporter sites and 5-HT1D sites, 5-HT1A and 5-HT2A receptors and the density of neurons and astrocytes will characterize target neuron integrity. Biological changes related to the duration or severity of alcoholism are consistent with alcohol toxicity; whereas changes independent of duration or severity of alcoholism but related to the age of onset might suggest a biological predisposition to alcoholism. The data gathered will suggest mechanisms involved in the pathogenesis of alcoholism. The demonstration of serotonergic neuropathology in the brain of alcoholics may suggest possible pharmacologic therapeutics and new diagnostic approaches using functional brain imaging.

描述：(改编自《调查者摘要》)5-羟色胺 酗酒者的缺乏症主要是基于观察而假定的 脑脊液中减少的5-羟色胺代谢物的疗效 5-羟色胺激动剂和摄取抑制剂在减少酒精消耗中的作用 酒精偏爱的人和动物模型及生化异常 老鼠品系。初步的尸检证据表明 中缝背核内5-羟色胺合成神经元和 前额叶皮质内5-羟色胺神经末梢的减少 酗酒者。对5-羟色胺系统的全面尸检研究是 建议确定酗酒者5-羟色胺系统的变化。至 进一步评估任何发现的意义，我们将确定 这些变化与酒精的持续时间或严重程度有关。 依赖。该提案已进行了广泛修改，以满足 对前一次审查的批评。 符合DSM-IV酒精滥用标准的20名受试者的大脑 将检查依赖和20个非精神控制组。酒精 虐待/依赖将通过心理尸检来诊断。 DRN 5-羟色胺神经元的计算机辅助体视学和形态计量学研究 酒精和酒精中抗苯丙氨酸羟基酶抗体标记 非精神病学对照将决定：数量、密度、分布 和DRN 5-羟色胺能神经元的形态作为神经退行性变的指标。 在腹外侧额叶皮质、初级运动皮质和视觉 大脑皮层5-羟色胺转运体和5-羟色胺1D的测定 和5-HT2a受体以及神经元和星形胶质细胞的密度 描述目标神经元的完整性。 与酒精中毒持续时间或严重程度相关的生物学变化有 与酒精毒性一致；而变化与持续时间或 酒精中毒的严重程度与发病年龄有关，可能表明 酗酒的生理倾向。 收集到的数据将提示与糖尿病发病有关的机制 酗酒。5-羟色胺能神经病理学在脑内的表现 可能会提出可能的药物疗法和新的 使用脑功能成像的诊断方法。