DORSAL RAPHE NUCLEUS SEROTONIN NEURONS IN ALCOHOLISM

描述：（改编自研究者摘要）血清素 酗酒者的缺陷主要是根据观察而假设的 降低脑脊髓液中5-羟色胺代谢物的含量， 5-羟色胺激动剂和摄取抑制剂在减少 人类和动物模型以及酒精偏好的生化异常 老鼠品系。初步尸检证据表明， 中缝背核（DRN）和背侧核（DRN）中的降钙素合成神经元 前额叶皮层中5-羟色胺神经末梢的数量减少 酗酒者。对血清素系统的全面死后研究是 研究酒精中毒者血清素系统的变化。到 进一步评估任何发现的重要性，我们将确定是否 这些变化与酒精的持续时间或严重程度有关 依赖该提案已被广泛修改，以满足 对以往审查的批评。 20名符合DSM-IV酒精滥用标准的受试者的大脑， 依赖和20个非精神病对照将进行检查。醇 滥用/依赖将通过心理解剖进行诊断。 计算机辅助DRN 5-羟色胺神经元的体视学和形态计量学研究 用抗苯丙氨酸羟化酶抗体标记酗酒者， 非精神病控制将确定：数量，密度，分布 和DRN神经元能神经元的形态作为神经变性的量度。 在腹外侧前额叶皮层、初级运动皮层和视觉皮层中， 皮质，5-羟色胺转运体位点和5-HT 1D位点的测量，5-HT 1A 和5-HT 2A受体以及神经元和星形胶质细胞的密度将 表征目标神经元完整性。 与酒精中毒的持续时间或严重程度相关的生物学变化是 与酒精毒性一致;而变化独立于持续时间或 酒精中毒的严重程度，但与发病年龄可能表明， 酗酒的生理倾向 所收集的数据将提示参与的发病机制， 酒精中毒脑内多巴胺能神经病理学的演示 酒精中毒者可能提示可能的药物治疗和新的 使用功能性脑成像的诊断方法。

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.