Genetic Relationship Between Ethanol-Induced Conditioned Place Preference and Other Ethanol Phenotypes in 15 Inbred Mouse Strains
Genetic Relationship Between Ethanol-Induced Conditioned Place Preference and Other Ethanol Phenotypes in 15 Inbred Mouse Strains
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DOI：
10.1037/a0036459
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发表时间：
2014-08-01
影响因子：
1.9
通讯作者：
Cunningham, Christopher L.
中科院分区：
文献类型：
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作者：
Cunningham, Christopher L.
用于衡量酒精的奖励或强化作用的不同行为之间的遗传关系知之甚少。为了解决这个问题，乙醇诱导的条件性位置偏爱（CPP）进行了测试，在遗传多样性小组的近交系小鼠品系，和品系的手段，从这项研究和其他近交系研究被用来检查CPP和几个乙醇相关的表型，包括活动测量记录在CPP训练和测试之间的遗传相关性。将来自每个品系的小鼠暴露于使用2或4 g/kg乙醇剂量的充分表征的无偏位置调节程序;在所有试验中，将来自每个品系的另外一组单独暴露于生理盐水。基因型对CPP、基础自发活动、乙醇刺激活动以及重复乙醇暴露对活动的影响有显著影响。相关性分析表明，CPP和甜乙醇摄入量之间的显着负遗传相关性和CPP和测试会话活动之间，以及CPP和慢性乙醇戒断严重程度之间的显着正遗传相关性。此外，CPP和乙醇诱导的条件性味觉厌恶之间存在正遗传相关的趋势。这些遗传相关性表明CPP和这些性状中的每一个的遗传机制是重叠的。遗传关系的模式表明，乙醇对饮酒的厌恶作用和乙醇对CPP的奖励作用有更大的影响。总的来说，这些数据支持基因型影响乙醇的奖励效应的想法，这可能是一个重要的因素，成瘾的脆弱性。
The genetic relationships between different behaviors used to index the rewarding or reinforcing effects of alcohol are poorly understood. To address this issue, ethanol-induced conditioned place preference (CPP) was tested in a genetically diverse panel of inbred mouse strains, and strain means from this study and other inbred strain studies were used to examine the genetic correlation between CPP and several ethanol-related phenotypes, including activity measures recorded during CPP training and testing. Mice from each strain were exposed to a well-characterized unbiased place conditioning procedure using ethanol doses of 2 or 4 g/kg; an additional group from each strain was exposed to saline alone on all trials. Genotype had a significant effect on CPP, basal locomotor activity, ethanol-stimulated activity, and the effect of repeated ethanol exposure on activity. Correlational analyses showed significant negative genetic correlations between CPP and sweetened ethanol intake and between CPP and test session activity, as well as a significant positive genetic correlation between CPP and chronic ethanol withdrawal severity. Moreover, there was a trend toward a positive genetic correlation between CPP and ethanol-induced conditioned taste aversion. These genetic correlations suggest overlap in the genetic mechanisms underlying CPP and each of these traits. The patterns of genetic relationships suggest a greater impact of ethanol's aversive effects on drinking and a greater impact of ethanol's rewarding effects on CPP. Overall, these data support the idea that genotype influences ethanol's rewarding effect, a factor that may contribute importantly to addictive vulnerability.