School of Life Sciences, Department of Physiology, Anatomy and Microbiology, La Trobe University, Australia.
School of Psychology and Public Health, Department of Psychology, La Trobe University, Australia.
Addict Biol. 2019 Sep;24(5):886-897. doi: 10.1111/adb.12641. Epub 2018 Jul 9.
Galanin is a neuropeptide which mediates its effects via three G-protein coupled receptors (GAL ). Administration of a GAL antagonist reduces alcohol self-administration in animal models while allelic variation in the GAL gene has been associated with an increased risk of alcohol use disorders in diverse human populations. Based on the association of GAL with alcoholism, we sought to characterize drug-seeking behavior in GAL -deficient mice for the first time. In the two-bottle free choice paradigm, GAL -KO mice consistently showed a significantly increased preference for ethanol over water when compared to wildtype littermates. Furthermore, male GAL -KO mice displayed significantly increased responding for ethanol under operant conditions. These differences in alcohol seeking behavior in GAL -KO mice did not result from altered ethanol metabolism. In contrast to ethanol, GAL -KO mice exhibited similar preference for saccharin and sucrose over water, and a similar preference for a high fat diet over a low fat diet as wildtype littermates. No differences in cognitive and locomotor behaviors were observed in GAL -KO mice to account for increased alcohol seeking behavior. Overall, these findings suggest genetic ablation of GAL in mice increases alcohol consumption.
甘丙肽是一种神经肽，通过三种 G 蛋白偶联受体 (GAL) 发挥作用。给予 GAL 拮抗剂可减少动物模型中的酒精自我给药，而 GAL 基因的等位基因变异与不同人群中酒精使用障碍的风险增加有关。基于 GAL 与酗酒的关联，我们首次试图描述 GAL 缺陷型小鼠的觅药行为。在双瓶自由选择范式中，与野生型同窝仔相比，GAL-KO 小鼠对乙醇的偏好明显增加。此外，雄性 GAL-KO 小鼠在操作性条件下对乙醇的反应明显增加。GAL-KO 小鼠在酒精觅药行为上的这些差异并非由于乙醇代谢的改变。与乙醇不同的是，GAL-KO 小鼠对糖精和蔗糖的偏好与水相似，对高脂肪饮食的偏好与野生型同窝仔相似。GAL-KO 小鼠在认知和运动行为上没有差异，无法解释其酒精觅药行为的增加。总体而言，这些发现表明，在小鼠中基因敲除 GAL 会增加酒精的摄入。
