Dorsal Raphe Nucleus Serotonergic Neurons in Alcoholism

超出所提供的空间。基于脑脊液中5 -羟色胺代谢物减少的报道，5 -羟色胺激动剂和摄取抑制剂在人类和动物模型中减少酒精消耗的功效，以及酒精偏好大鼠品系的生化异常，我们假设了酗酒者脑干和大脑皮层中的5 -羟色胺异常。在资助期内取得了相当大的进展，并获得了酗酒者中缝背核（DRN）中血清素合成神经元改变的死后证据，包括神经元过程密度增加。在前额叶皮层，与对照组相比，酗酒者的血清素受体没有明显变化。建立了一种新的免疫自显影方法，用于定量冷冻脑干切片中的色氨酸羟化酶。我们建议对冷冻脑干和前脑的5 -羟色胺系统进行一系列全面的死后研究，以进一步研究DRN中的5 -羟色胺源神经元以及外侧和眶额叶皮层和前扣带中的5 -羟色胺靶神经元。将对符合DSM-IV酒精滥用或依赖标准和非精神控制标准的20对匹配（年龄、性别、种族、死亡间隔）病例的大脑进行检查。酒精滥用/依赖将通过心理解剖根据DSM-IV标准进行诊断。在DRN中，色氨酸羟化酶将使用免疫放射自显影在整个DRN（放射自显影）和单个神经元（乳状液）水平上进行测量；在相邻的切片中，5-羟色胺、前体和代谢物将在DRN中测量（HPLC）， 5-羟色胺转运体（SERT）位点和5-HT1A自身受体在DRN中的结合将通过定量放射自显影法测量。在腹外侧和眶前额叶皮层、前扣带皮层和初级运动皮层，测量皮质神经元密度将使用立体学来确定，神经元密度将与5-羟色胺转运体位点、5- ht1a和5-HT2A受体在同一皮质区域的浓度相关，从而得出每个神经元的受体浓度指数。这些研究旨在评估酗酒者前额叶皮层中drn - 5 -羟色胺神经元和神经元的完整性。这些研究的结果应该有助于澄清5 -羟色胺受体或神经元是否调节或不调节酗酒者。网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. Serotonin abnormalities in the brainstem and cerebral cortex of alcoholics is hypothesized based on reports of reduced serotonin metabolites inthe cerebrospinal fluid, the efficacyof serotonin agonists and uptake inhibitors in reducingalcoholconsumption inhumansandanimal models andbiochemical abnormalities inalcohol preferring rat strains. During the funded period considerable progress was made and postmortem evidence of alterations in serotonin-synthesizing neurons in the dorsal raphe nucleus (DRN) of alcoholics, including increased densityof neuronal processes, was obtained. In the prefrontal cortex, serotonin receptors were not markedly changed in alcoholics compared to matched controls. A novel immunoautoradiographic method was developed for quantifying tryptophan hydroxylase in frozen brainstem sections. A comprehensive series of postmortem studies of the serotonin system in frozen brainstem and forebrain is proposed to further examine serotonin source neurons in the DRN and target neurons in the lateral and orbital prefrontal cortex and in the anterior cingulate. The brain of 20 matched (age, sex, race, postmortem interval) pairs of cases with DSM-IV criteria for alcoho abuse or dependence and nonpsychiatric controlswill beexamined. Alcohol abuse/dependence will be diagnosed accordingto DSM-IV criteria bypsychological autopsy. Inthe DRN: tryptophan hydroxylase will be measured using immunoautoradiography at the level of the entire DRN (autoradiography) and in individual neurons (emulsion); in adjacent sections, 5-HT, precursors and metabolites will be measured in DRN punches (HPLC), and Serotonin transporter (SERT) sites and 5-HT1A autoreceptor binding in the DRN will be measured by quantitative autoradiography. In the ventrolateral and orbital prefrontal cortex, anterior cingulate and primary motor cortex, measurement of cortical neuron density will be determined using stereology and neuron density will be related to the concentration of serotonin transporter sites, 5-HT1Aand 5-HT2A receptors in the same cortical regionstoderive an index of the concentration of receptors per neuron. The studies are designed to assess the integrity of DRNserotonin neurons and neurons in the prefrontalcortex in alcoholics. The results of the studies should help to clarify whether serotonin receptors or neurons regulate or fail to regulate in alcoholics. PERFORMANCE SITE ========================================Section End===========================================