Behavioral phenotypes revealed during reversal learning are linked with novel genetic loci in diversity outbred mice

Autor: Jared R. Bagley, Lauren S. Bailey, Leona H. Gagnon, Hao He, Vivek M. Philip, Laura G. Reinholdt, Lisa M. Tarantino, Elissa J. Chesler, James D. Jentsch
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Addiction Neuroscience, Vol 4, Iss , Pp 100045- (2022)
Druh dokumentu: article
ISSN: 2772-3925
DOI: 10.1016/j.addicn.2022.100045
Popis: Impulsive behavior and impulsivity are heritable phenotypes that are strongly associated with risk for substance use disorders. Identifying the neurogenetic mechanisms that influence impulsivity may also reveal novel biological insights into addiction vulnerability. Our past studies using the BXD and Collaborative Cross (CC) recombinant inbred mouse panels have revealed that behavioral indicators of impulsivity measured in a reversal-learning task are heritable and are genetically correlated with aspects of intravenous cocaine self-administration. Genome-wide linkage studies in the BXD panel revealed a quantitative trait locus (QTL) on chromosome 10, but we expect to identify additional QTL by testing in a population with more genetic diversity. To this end, we turned to Diversity Outbred (DO) mice; 392 DO mice (156 males, 236 females) were phenotyped using the same reversal learning test utilized previously. Our primary indicator of impulsive responding, a measure that isolates the relative difficulty mice have with reaching performance criteria under reversal conditions, revealed a genome-wide significant QTL on chromosome 7 (max LOD score = 8.73, genome-wide corrected p
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