Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas.
Department of Neuroscience, The Scripps Research Institute, La Jolla, California.
Genes Brain Behav. 2019 Jul;18(6):e12562. doi: 10.1111/gbb.12562. Epub 2019 May 2.
The voltage-gated sodium channel subunit β4 (SCN4B) regulates neuronal activity by modulating channel gating and has been implicated in ethanol consumption in rodent models and human alcoholics. However, the functional role for Scn4b in ethanol-mediated behaviors is unknown. We determined if genetic global knockout (KO) or targeted knockdown of Scn4b in the central nucleus of the amygdala (CeA) altered ethanol drinking or related behaviors. We used four different ethanol consumption procedures (continuous and intermittent two-bottle choice (2BC), drinking-in-the dark and chronic intermittent ethanol vapor) and found that male and female Scn4b KO mice did not differ from their wild-type (WT) littermates in ethanol consumption in any of the tests. Knockdown of Scn4b mRNA in the CeA also did not alter 2BC ethanol drinking. However, Scn4b KO mice showed longer duration of the loss of righting reflex induced by ethanol, gaboxadol, pentobarbital and ketamine. KO mice showed slower recovery to basal levels of handling-induced convulsions after ethanol injection, which is consistent with the increased sedative effects observed in these mice. However, Scn4b KO mice did not differ in the severity of acute ethanol withdrawal. Acoustic startle responses, ethanol-induced hypothermia and clearance of blood ethanol also did not differ between the genotypes. There were also no functional differences in the membrane properties or excitability of CeA neurons from Scn4b KO and WT mice. Although we found no evidence that Scn4b regulates ethanol consumption in mice, it was involved in the acute hypnotic effects of ethanol and other sedatives.
电压门控钠离子通道亚基 β4（SCN4B）通过调节通道门控来调节神经元活动，并且在啮齿动物模型和人类酗酒者中与乙醇消耗有关。然而，Scn4b 在乙醇介导的行为中的功能作用尚不清楚。我们确定了中央杏仁核（CeA）中 Scn4b 的遗传全局敲除（KO）或靶向敲低是否改变了乙醇的摄取或相关行为。我们使用了四种不同的乙醇消耗程序（连续和间歇性双瓶选择（2BC）、暗饮和慢性间歇性乙醇蒸气），发现雄性和雌性 Scn4b KO 小鼠在任何测试中都与野生型（WT）同窝仔在乙醇消耗上没有差异。CeA 中的 Scn4b mRNA 敲低也没有改变 2BC 乙醇的摄取。然而，Scn4b KO 小鼠在乙醇、gaboxadol、戊巴比妥和氯胺酮诱导的翻正反射丧失持续时间较长。KO 小鼠在乙醇注射后恢复到基础水平的处理诱导性抽搐的速度较慢，这与这些小鼠中观察到的镇静作用增强一致。然而，Scn4b KO 小鼠在急性乙醇戒断的严重程度上没有差异。听觉惊吓反应、乙醇诱导的体温过低和血液乙醇清除率在基因型之间也没有差异。Scn4b KO 和 WT 小鼠的 CeA 神经元的膜特性或兴奋性也没有功能差异。尽管我们没有发现 Scn4b 调节小鼠乙醇摄取的证据，但它参与了乙醇和其他镇静剂的急性催眠作用。
