Taurine: EtOH Withdrawal Attenuation via AVP Moduation

描述（由申请人提供）：乙醇引起的神经系统变化会产生厌恶的戒断症状，​​通常会促进进一步的乙醇滥用，以此作为抑制这些不良状况的一种方式。治疗酗酒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事件的可能性。尽管迄今为止，大多数酒精研究主要集中在乙醇引起的谷氨酸稳态破坏上，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影响因素。然而，β-氨基酸牛磺酸在渗透压调节和钙调节方面具有公认的功能，可能会改善这些由乙醇引发的变化并降低总体戒断严重程度。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，通过对通过连续和间歇蒸气吸入方法产生乙醇依赖性的雄性 C3H 小鼠戒断引起的癫痫发作的测量来确定。此外，在戒断严重程度达到峰值的时间点，对全身渗透压的主要神经内分泌调节剂精氨酸加压素（AVP）进行定量，将确定下丘脑和血浆 AVP 水平的任何变化是否与戒断严重程度相对应。此外，这些研究还将评估暴露于乙醇、接受牛磺酸处理的组是否表现出与未接受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支持牛磺酸治疗酗酒的证据。

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.