Kapfhamer D, Bettinger J C, Davies A G, Eastman C L, Smail E A, Heberlein U, McIntire S L
The Ernest Gallo Clinic and Research Center, University of California at San Francisco, Emeryville, CA 94608, USA.
Genes Brain Behav. 2008 Aug;7(6):669-76. doi: 10.1111/j.1601-183X.2008.00404.x. Epub 2008 Apr 7.
The mechanisms by which ethanol induces changes in behavior are not well understood. Here, we show that Caenorhabditis elegans loss-of-function mutations in the synaptic vesicle-associated RAB-3 protein and its guanosine triphosphate exchange factor AEX-3 confer resistance to the acute locomotor effects of ethanol. Similarly, mice lacking one or both copies of Rab3A are resistant to the ataxic and sedative effects of ethanol, and Rab3A haploinsufficiency increases voluntary ethanol consumption. These data suggest a conserved role of RAB-3-/RAB3A-regulated neurotransmitter release in ethanol-related behaviors.
乙醇引起行为变化的机制尚未完全明确。在此，我们表明，秀丽隐杆线虫中与突触小泡相关的RAB - 3蛋白及其鸟苷三磷酸交换因子AEX - 3的功能缺失突变赋予了对乙醇急性运动效应的抗性。同样，缺乏一个或两个Rab3A拷贝的小鼠对乙醇的共济失调和镇静作用具有抗性，并且Rab3A单倍体不足会增加自愿乙醇消耗量。这些数据表明RAB - 3 / RAB3A调节的神经递质释放在乙醇相关行为中具有保守作用。
