ALCOHOL, AGING, SEROTONERGIC PROBES, AND TREATMENT MATCHING

酒精、衰老、血清素探针和治疗匹配

• 批准号: 5204242
• 负责人: ALAN M MELLOW
• 金额: --
• 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/5204242
• 关键词: aging; alcoholic beverage consumption; alcoholism /alcohol abuse; alcoholism /alcohol abuse chemotherapy; antidepressants; blood chemistry; cerebrospinal fluid; clinical trials; cortisol; fluoxetine; high performance liquid chromatography; human middle age (35-64); human old age (65+); human subject; human therapy evaluation; hydroxyindoleacetate; mental disorder diagnosis; neurochemistry; piperazines; prolactin; psychological tests; radioimmunoassay; serotonin; serotonin inhibitor; young adult human (21-34)

The treatment of alcoholism is often complex and problematic. There is growing recognition that no single treatment is effective for all individuals and that treatment matching may be vital. Thus optimum treatment should include vigorous psychosocial interventions, and whether indicated, specific biological therapies targeted to underlying pathophysiology. There is considerable evidence for a role for the monamine neurotransmitter serotonin (5-HT) in both the regulation of alcohol intake and as a biological selective serotonin reuptake inhibitors (SSRI) in the reduction of alcohol intake and maintenance of abstinence in alcoholics. However, little is known about the clinical or biological characteristics that would identify those alcoholic patients who might benefit from SSRI treatment. Thus, treatment matching is still not possible. Furthermore, nothing is known about those relationship in older alcoholics, a population which might benefit greatly from a safe, effective medical therapy. The long-term objectives of this project are to gain new information on the role of alterations in serotonin (5-HT) function in the pathophysiology, clinical features and pharmacotherapy of alcoholism. The specific aims are: (1) characterization of serotonin function in alcoholic patients, (2) a controlled trial of the efficacy of serotonergic treatment with the SSRI fluoxetine in reducing alcohol intake in alcoholic patients, (3) correlation of serotonergic measures with clinical response to fluoxetine treatment, and (4) examination of the effects of aging on serotonin function and clinical response to fluoxetine in alcoholic patients. It is proposed to measure cerebrospinal fluid (CSF) 5-hydroxyindoleacetic (5-HIAA, the major serotonin metabolite) levels in newly detoxified alcoholics and age- and sex-matched normal controls, as well as plasma prolactin, cortisol, vital signs, and behavioral state after a single intravenous infusion ("challenge" strategy) of m-chlorophenylpiperazine (m--CPP, a serotonin agonist) in detoxified alcoholics and age- and sex-matched normal controls. Patients will then undergo a trial comparing the efficacy of fluoxetine, with placebo, in decreasing alcohol intake in a twelve-week, double-blind, parallel design, randomized controlled trial, during which alcohol craving, use, and other related variables will be monitored. Serotonin function measures at baseline will then be correlated with clinical response in those alcoholic patients receiving fluoxetine treatment. A sub-analysis will examine these correlations in older (>age 55) vs. younger (<age55) patients. It is hoped that this work will lead to greater understanding of the biochemical pathogenesis of alcoholism, as well as improved treatment matching and more specific and effective treatment for alcoholism, particularly for the elderly.

酒精中毒的治疗通常是复杂而有问题的。 有 越来越认识到没有单一治疗对所有人有效 个人和治疗匹配可能至关重要。 因此最佳 治疗应包括有力的社会心理干预措施，以及是否 指示针对基础的特定生物疗法 病理生理学。 有大量证据表明 在两种调节中 酒精摄入量和作为生物选择性5-羟色胺再摄取 抑制剂（SSRI）减少酒精摄入量和维持 戒酒。 但是，关于临床知之甚少 或生物学特征，可以识别那些酒精 可能受益于SSRI治疗的患者。 因此，治疗匹配 仍然不可能。 此外，对那些人一无所知 老年酗酒者的关系，可能受益的人口 大大来自安全有效的医疗疗法。 该项目的长期目标是获取有关的新信息 在5-羟色胺（5-HT）功能中的改变在 病理生理学，临床特征和酒精中毒药物疗法。 具体目的是：（1）5-羟色胺功能的表征 酒精患者，（2）对疗效的对照试验 用SSRI氟西汀治疗血清素能治疗，以减少酒精 酒精患者的摄入量，（3）血清素能测量的相关性 对氟西汀治疗的临床反应，以及（4）检查 衰老对5-羟色胺功能的影响以及对 酒精患者的氟西汀。 提议测量 脑脊液（CSF）5-羟基丁乙酸酯（5-HIAA，主要 新排毒的酗酒者以及年龄和年龄和年龄和年龄的羟色胺代谢物）水平 性别匹配的正常对照以及血浆催乳素，皮质醇，重要 一次静脉输注后的迹象和行为状态 （“挑战”策略）M-氯苯基哌嗪（M--CPP，5-羟色胺 激动剂）在排毒的酗酒者以及年龄和性别匹配的正常 控件。 然后，患者将进行比较的试验 氟西汀，安慰剂，减少十二周的酒精摄入量， 双盲，平行设计，随机对照试验，在此期间 将监测酒精渴望，使用和其他相关变量。 然后，基线时的5-羟色胺功能度量将与 那些接受氟西汀的酒精患者的临床反应 治疗。 亚分​​析将检查较老的这些相关性（>年龄 55）vs.（<Age55）患者。希望这项工作能够领导 为了更了解酒精中毒的生化发病机理， 以及改进的治疗匹配和更具体和有效的 酒精中毒的治疗，特别是对于老年人。