Taurine: EtOH Withdrawal Attenuation via AVP Moduation

描述(由申请人提供)：乙醇诱导的神经变化会产生令人厌恶的戒断症状，这往往会促进进一步的酒精滥用，以此作为抑制这些有害条件的一种方式。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，以便有效地减少进一步滥用的可能性。尽管到目前为止，大多数酒精研究主要集中在乙醇诱导的谷氨酸稳态的破坏上，但全身渗透压的神经内分泌控制的变化似乎也是戒断严重程度的一个促成因素。然而，具有渗透调节和钙调节功能的β-氨基酸牛磺酸可能会改善这些由乙醇引起的改变，并降低整体戒断的严重程度。这项拟议的研究将检验牛磺酸治疗在降低酒精戒断严重程度方面的能力，通过连续和间歇蒸汽吸入方法使酒精依赖的雄性C3H小鼠的抽搐发作的衡量标准来确定。此外，在戒断严重程度最严重的时间点，对全身渗透压的主要神经内分泌调节因子精氨酸加压素(AVP)的定量将决定下丘脑和血浆AVP水平的变化是否与戒断严重程度相对应。此外，这些研究还将评估酒精暴露、牛磺酸处理组的AVP水平是否与那些没有牛磺酸处理的乙醇组不同。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作用。

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.