Taurine: EtOH Withdrawal Attenuation via AVP Moduation

牛磺酸：通过 AVP 调节减弱乙醇戒断作用

• 批准号: 7102848
• 负责人: ANDRE W ZALUD
• 金额: $ 0.57万
• 依托单位: BAYLOR UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2006-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7102848
• 关键词: alcoholism /alcohol abuse chemotherapy; alcoholism /alcohol abuse therapy; arginine vasopressin; drug administration rate /duration; drug withdrawal; ethanol; genetically modified animals; high performance liquid chromatography; hormone metabolism; hormone regulation /control mechanism; laboratory mouse; neural transmission; neurohormones; neuroprotectants; neurotoxicology; neurotransmitter metabolism; nonhuman therapy evaluation; plasma; predoctoral investigator; radioimmunoassay; supraoptic nucleus; taurine

DESCRIPTION (provided by applicant): Ethanol-induced neurological changes produce aversive withdrawal symptoms that often promote further ethanol abuse as a way of suppressing these unwanted conditions. Efforts to treat alcoholism must address the pervasive physiological alterations that result in withdrawal symptoms in order to effectively reduce the probability of further abuse episodes. Although most alcohol research, to date, has focused primarily upon ethanol-induced disruptions in glutamate homeostasis, changes in the neuroendocrine control of systemic osmolarity also appears to exist as a contributing factor of withdrawal severity. However, the beta-amino acid taurine, with recognized functions in osmoregulation and calcium modulation, might ameliorate these ethanol-provoked alterations and reduce overall withdrawal severities. This proposed investigation will examine the ability of taurine treatment in reducing ethanol withdrawal severity, determined by measures of withdrawal-induced seizures, in male C3H mice made ethanol dependent through both continuous and intermittent vapor inhalation methods. In addition, during time points of peak withdrawal severity, quantification of the major neuroendocrine regulator of systemic osmolarity, arginine vasopressin (AVP), will determine whether any changes in hypothalamic and plasma AVP levels correspond to the degree of withdrawal severity. Furthermore, these studies will also assess whether ethanol-exposed, taurine-treated groups display AVP levels different from those ethanol groups without taurine treatment. As a result, data collected from these studies could provide evidence that supports the therapeutic use of taurine in alcoholism.

描述（由申请人提供）：乙醇诱导的神经系统变化会产生令人厌恶的戒断症状，这些症状通常会促进进一步的乙醇滥用，作为抑制这些不良症状的一种方式。治疗酒精中毒的努力必须解决导致戒断症状的普遍生理变化，以有效降低进一步滥用发作的可能性。虽然大多数酒精的研究，到目前为止，主要集中在乙醇引起的谷氨酸体内平衡的破坏，在神经内分泌控制的全身渗透压的变化似乎也存在作为一个因素的戒断严重程度。然而，β-氨基酸牛磺酸，具有公认的功能，在酒精调节和钙调节，可能会改善这些乙醇引起的变化，并降低整体戒断严重程度。这项拟议的研究将检查牛磺酸治疗降低乙醇戒断严重程度的能力，通过戒断诱导癫痫发作的措施确定，通过连续和间歇蒸汽吸入方法使乙醇依赖的雄性C3 H小鼠。此外，在戒断严重程度峰值的时间点，全身渗透压的主要神经内分泌调节剂精氨酸加压素（AVP）的定量将确定下丘脑和血浆AVP水平的任何变化是否对应于戒断严重程度。此外，这些研究还将评估乙醇暴露、牛磺酸处理组是否显示出与未进行牛磺酸处理的乙醇组不同的AVP水平。因此，从这些研究中收集的数据可以提供证据，支持牛磺酸在酒精中毒中的治疗用途。