Heritable variation in locomotion, reward sensitivity and impulsive behaviors in a genetically diverse inbred mouse panel.
Heritable variation in locomotion, reward sensitivity and impulsive behaviors in a genetically diverse inbred mouse panel.
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DOI：
10.1111/gbb.12773
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Jentsch JD
中科院分区：
文献类型：
--
作者：
Bailey LS;Bagley JR;Dodd R;Olson A;Bolduc M;Philip VM;Reinholdt LG;Sukoff Rizzo SJ;Tarantino L;Gagnon L;Chesler EJ;Jentsch JD
包括酒精和可卡因等兴奋剂在内的滥用药物产生的影响受到个体差异的影响，而基因差异至少是这些差异的一部分。值得注意的是，在动物模型和人类受试者中的研究都指出，奖励敏感性和冲动是预测对兴奋剂药物相对更积极的主观反应的特征特征。在这里，我们描述了使用8个合作交叉(CC)创始人品系和38个(反向学习)或10个(所有其他测试)CC品系来检验奖励敏感性和冲动特征的遗传力，以及这些指标与现有成瘾相关表型之间的遗传相关性。方法：研究方法。所有菌株都在开阔的野外活动和奖励敏感性(摄入巧克力Boost®)进行了测试。然后将小鼠分为两组，分别进行反转学习(冲动行为和等待冲动)或延迟打折(冲动选择)。结果。CC和方正小鼠在冲动行为、冲动选择、等待冲动、运动活动和奖励敏感性方面表现出显著的遗传力，每一种冲动表型都被确定为不相关的独立特征。这项研究是在系统神经遗传学成瘾中心(CSNA)更广泛的实验室间工作中进行的，目的是表征CC和DO小鼠的多个可卡因滥用相关特征。这些数据将有助于发现预测性特征之间的遗传相关性，从而指导发现导致成瘾行为的基因和遗传变异。
Drugs of abuse, including alcohol and stimulants like cocaine, produce effects that are subject to individual variability, and genetic variation accounts for at least a portion of those differences. Notably, research in both animal models and human subjects point towards reward sensitivity and impulsivity as being trait characteristics that predict relatively greater positive subjective responses to stimulant drugs. Here we describe use of the eight Collaborative Cross (CC) founder strains and thirty-eight (reversal learning) or ten (all other tests) CC strains to examine the heritability of reward sensitivity and impulsivity traits, as well as genetic correlations between these measures and existing addiction-related phenotypes. Methods. Strains were all tested for activity in an open field and reward sensitivity (intake of chocolate BOOST®). Mice were then divided into two counterbalanced groups and underwent reversal learning (impulsive action and waiting impulsivity) or delay discounting (impulsive choice). Results. CC and founder mice demonstrate significant heritability for impulsive action, impulsive choice, waiting impulsivity, locomotor activity, and reward sensitivity, with each impulsive phenotype determined to be non-correlating, independent traits. This research was conducted within the broader, inter-laboratory effort of the Center for Systems Neurogenetics of Addiction (CSNA) to characterize CC and DO mice for multiple, cocaine abuse related traits. These data will facilitate the discovery of genetic correlations between predictive traits, which will then guide discovery of genes and genetic variants that contribute to addictive behaviors.
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影响因子：
5.9
作者：
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通讯作者：
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影响因子：
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作者：
Enoch, Mary-Anne
通讯作者：
Enoch, Mary-Anne
影响因子：
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作者：
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通讯作者：
Nouvion, Sylvain O.