Erwin V G, Radcliffe R A, Gehle V M, Jones B C
Alcohol Research Center and School of Pharmacy, University of Colorado Health Sciences Center, Denver 80262, USA.
J Pharmacol Exp Ther. 1997 Feb;280(2):919-26.
We have analyzed LSXSS recumbinant inbred for ethanol-induced activity using 2.0 g/kg ethanol and a new method we call ethanol activation slope. The ethanol activation slope provides a robust dose-response measure of ethanol activation, independent of both activity after saline and the inhibitory effects of ethanol on locomotor activity. These behavioral data were used in a quantitative trait locus analysis to map chromosomal loci involved in ethanol-induced locomotor activity. We tentatively identified seven loci that mediate the low-dose stimulatory effect of ethanol and six loci involved in locomotion after 2.0 g/kg ethanol. Only one of the loci are in common between the two behaviors. We also compared the behavioral quantitative trait locus to those previously identified that are involved in regulating central nervous system neurotensin levels and neurotensin receptor densities. Six chromosomal regions were identified that regulate at least one central nervous system neurotensin measure and an ethanol-induced locomotor behavior. The identification of loci controlling both central nervous system neurotensin levels or neurotensin receptor densities and ethanol-induced locomotor activity strengthens the proposal that neurotensin regulates, in part, ethanol-induced behaviors and central nervous system sensitivity to ethanol.
我们使用2.0克/千克乙醇以及一种我们称为乙醇激活斜率的新方法，分析了LSXSS重组近交系小鼠对乙醇诱导活动的反应。乙醇激活斜率提供了一种可靠的乙醇激活剂量反应测量方法，该方法不受生理盐水处理后的活动以及乙醇对运动活动的抑制作用的影响。这些行为数据被用于数量性状基因座分析，以绘制参与乙醇诱导运动活动的染色体基因座。我们初步确定了七个介导乙醇低剂量刺激作用的基因座，以及六个与2.0克/千克乙醇处理后的运动有关的基因座。这两种行为之间只有一个基因座相同。我们还将行为数量性状基因座与先前确定的参与调节中枢神经系统神经降压素水平和神经降压素受体密度的基因座进行了比较。确定了六个染色体区域，这些区域调节至少一种中枢神经系统神经降压素指标以及乙醇诱导的运动行为。控制中枢神经系统神经降压素水平或神经降压素受体密度以及乙醇诱导运动活动的基因座的确定，进一步支持了神经降压素部分调节乙醇诱导行为和中枢神经系统对乙醇敏感性的观点。
