Newton P M, Messing R O
Ernest Gallo Clinic and Research Center, Department of Neurology, University of California, San Francisco, CA, USA.
Behav Neurosci. 2007 Apr;121(2):439-42. doi: 10.1037/0735-7044.121.2.439.
Determining the intracellular signaling pathways that mediate the rewarding effects of ethanol may help identify drug targets to curb excessive alcohol consumption. Mice lacking the epsilon isoform of protein kinase C (PKCepsilon) voluntarily consumed less ethanol than wild-type mice in two-bottle choice and operant self-administration assays. Decreased consumption may reflect either increased or decreased sensitivity to the rewarding effects of ethanol. Alternatively, decreased voluntary consumption may reflect a change in sensitivity to the aversive effects of ethanol. The authors used place conditioning to determine that PKCepsilon null mice have an increased sensitivity to the aversive effects of ethanol but a decreased sensitivity to the rewarding effects of ethanol. Together these data suggest that PKCepsilon null mice voluntarily consume less ethanol because they derive less reward and are more sensitive to the aversive effects of ethanol.
确定介导乙醇奖赏效应的细胞内信号通路，可能有助于识别抑制过度饮酒的药物靶点。在双瓶选择和操作性自我给药试验中，缺乏蛋白激酶Cε（PKCε）同工型的小鼠比野生型小鼠自愿摄入的乙醇更少。乙醇摄入量的减少可能反映出对乙醇奖赏效应的敏感性增加或降低。或者，自愿摄入量的减少可能反映出对乙醇厌恶效应的敏感性发生了变化。作者采用条件性位置偏好试验来确定，PKCε基因敲除小鼠对乙醇的厌恶效应敏感性增加，但对乙醇的奖赏效应敏感性降低。这些数据共同表明，PKCε基因敲除小鼠自愿摄入的乙醇较少，是因为它们获得的奖赏较少，并且对乙醇的厌恶效应更敏感。
