Sensitivity to the locomotor stimulant effects of ethanol and allopregnanolone is influenced by common genes
Sensitivity to the locomotor stimulant effects of ethanol and allopregnanolone is influenced by common genes
复制标题
DOI：
10.1037//0735-7044.116.1.126
复制
发表时间：
2002-02-01
影响因子：
1.9
通讯作者：
Phillips, TJ
中科院分区：
文献类型：
--
作者：
Palmer, AA;Miller, MN;Phillips, TJ
别孕烯醇酮是一种神经活性类固醇，像乙醇（EtOH）一样，具有兴奋剂，抗焦虑，共济失调和镇静作用。两个实验验证了这一假设，即对这些药物的运动刺激作用的敏感性受到一组共同基因的影响。在24个BXD重组近交系（RI）菌株中测定了对别孕烯醇酮的运动刺激作用的敏感性。菌株平均值与20个相同菌株中EtOH刺激的现存平均值呈正相关。数量性状基因座（QTL）分析暂时确定了许多基因座，包括几个已知的影响敏感性乙醇。在FAST和SLOW小鼠中也测量了对别孕烯醇酮的敏感性，这些小鼠被选择性地繁殖用于对EtOH的差异运动反应，以确定选择是否也改变了别孕烯醇酮的敏感性。与SLOW小鼠相比，FAST小鼠对别孕烯醇酮的刺激作用更敏感。这些数据表明，这些药物的运动刺激作用的敏感性是由共同的基因的影响。
Allopregnanolone is a neuroactive steroid that, like ethanol (EtOH), has stimulant, anxiolytic, ataxic, and depressant effects. Two experiments tested the hypothesis that sensitivity to the locomotor stimulant effects of these drugs is influenced by a common set of genes. Sensitivity to the locomotor stimulant effects of allopregnanolone was determined in 24 BXD recombinant inbred (RI) strains. Strain means were positively correlated with extant means for EtOH stimulation in 20 of the same strains. Quantitative trait locus (QTL) analysis provisionally identified many loci, including several known to influence sensitivity to EtOH. Sensitivity to allopregnanolone was also measured in FAST and SLOW mice, which were selectively bred for differential locomotor response to EtOH, to determine whether selection has also altered allopregnanolone sensitivity. FAST mice were more sensitive to the stimulant effects of allopregnanolone compared with SLOW mice. These data suggest that sensitivity to the locomotor stimulant effects of these drugs is influenced by common genes.