Divergent risky decision-making and impulsivity behaviors in Lewis rat substrains with low genetic difference.
Divergent risky decision-making and impulsivity behaviors in Lewis rat substrains with low genetic difference.
复制标题
遗传差异较小的 Lewis 大鼠亚系存在不同的风险决策和冲动行为。
DOI：
10.1037/bne0000557
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发表时间：
2023
影响因子：
1.9
通讯作者：
Simon,NicholasW
中科院分区：
文献类型：
--
作者：
Gabriel,DanielBK;Liley,AnnaE;Franks,HunterT;Minnes,GraceL;Tutaj,Monika;Dwinell,MelindaR;deJong,TristanV;Williams,RobertW;Mulligan,MeganK;Chen,Hao;Simon,NicholasW
物质使用障碍（SUD）与一组认知障碍相关，这些认知障碍导致对持续药物寻求和复发的脆弱性。其中两种内在表型--冒险决策和冲动--在SUD患者中被放大，并因反复接触非法药物而增强。识别这些行为模式变异的遗传因素对于SUD易感个体的早期识别、预防和治疗至关重要。在这里，我们比较了两个完全近交系的刘易斯大鼠-LEW/NCrl和LEW/NHsd之间的风险决策和冲动的不同方面。我们对这两种亚型进行了全基因组测序，以鉴定几乎所有相关的变体。我们观察到风险决策和冲动行为的实质性差异。相对于LEW/NHsd，LEW/NCrl亚株在决策任务中接受更高风险的选项，并且在低反应率任务的差异强化中接受更高的过早反应率。这些表型差异在女性中比男性更明显。我们在40×全基因组短读覆盖率下定义了这些亚株之间总共109，000个多态性。大约一半的变异位于8号染色体的单个1.5 Mb区域内，但没有影响蛋白质编码区。相比之下，其他变异广泛分布，其中38种被预测会导致蛋白质编码变异。总之，刘易斯大鼠亚系在冒险性和冲动性方面存在显著差异，只有少数容易定位的变异可能是因果关系。测序与降低复杂性的交叉相结合，应该能够识别一个或多个潜在的多种复杂成瘾相关行为的变体。（PsycInfo数据库记录（c）2023阿帕，保留所有权利）
Substance use disorder (SUD) is associated with a cluster of cognitive disturbances that engender vulnerability to ongoing drug seeking and relapse. Two of these endophenotypes—risky decision-making and impulsivity—are amplified in individuals with SUD and are augmented by repeated exposure to illicit drugs. Identifying genetic factors underlying variability in these behavioral patterns is critical for early identification, prevention, and treatment of SUD-vulnerable individuals. Here, we compared risky decision-making and different facets of impulsivity between two fully inbred substrains of Lewis rats—LEW/NCrl and LEW/NHsd. We performed whole genome sequencing of both substrains to identify almost all relevant variants. We observed substantial differences in risky decision-making and impulsive behaviors. Relative to LEW/NHsd, the LEW/NCrl substrain accepts higher risk options in a decision-making task and higher rates of premature responses in the differential reinforcement of low rates of responding task. These phenotypic differences were more pronounced in females than males. We defined a total of∼ 9,000 polymorphisms between these substrains at 40× whole genome short-read coverage. Roughly half of variants are located within a single 1.5 Mb region of Chromosome 8, but none impact protein-coding regions. In contrast, other variants are widely distributed, and of these, 38 are predicted to cause protein-coding variants. In conclusion, Lewis rat substrains differ significantly in risk-taking and impulsivity and only a small number of easily mapped variants are likely to be causal. Sequencing combined with a reduced complexity cross should enable identification of one or more variants underlying multiple complex addiction-relevant behaviors.(PsycInfo Database Record (c) 2023 APA, all rights reserved)