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

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 an...

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Autores principales: Bagley, Jared R., Bailey, Lauren S., Gagnon, Leona H., He, Hao, Philip, Vivek M., Reinholdt, Laura G., Tarantino, Lisa M., Chesler, Elissa J., Jentsch, James D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9879139/
https://www.ncbi.nlm.nih.gov/pubmed/36714272
http://dx.doi.org/10.1016/j.addicn.2022.100045
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author Bagley, Jared R.
Bailey, Lauren S.
Gagnon, Leona H.
He, Hao
Philip, Vivek M.
Reinholdt, Laura G.
Tarantino, Lisa M.
Chesler, Elissa J.
Jentsch, James D.
author_facet Bagley, Jared R.
Bailey, Lauren S.
Gagnon, Leona H.
He, Hao
Philip, Vivek M.
Reinholdt, Laura G.
Tarantino, Lisa M.
Chesler, Elissa J.
Jentsch, James D.
author_sort Bagley, Jared R.
collection PubMed
description 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<0.05). A measure of premature responding akin to that implemented in the 5-choice serial reaction time task yielded a suggestive QTL on chromosome 17 (max LOD score = 9.14, genome-wide corrected <0.1). Candidate genes were prioritized (2900076A07Rik, Wdr73 and Zscan2) based upon expression QTL data we collected in DO and CC mice and analyses using publicly available gene expression and phenotype databases. These findings may advance understanding of the genetics that drive impulsive behavior and enhance risk for substance use disorders.
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spelling pubmed-98791392023-01-26 Behavioral phenotypes revealed during reversal learning are linked with novel genetic loci in diversity outbred mice Bagley, Jared R. Bailey, Lauren S. Gagnon, Leona H. He, Hao Philip, Vivek M. Reinholdt, Laura G. Tarantino, Lisa M. Chesler, Elissa J. Jentsch, James D. Addict Neurosci Article 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<0.05). A measure of premature responding akin to that implemented in the 5-choice serial reaction time task yielded a suggestive QTL on chromosome 17 (max LOD score = 9.14, genome-wide corrected <0.1). Candidate genes were prioritized (2900076A07Rik, Wdr73 and Zscan2) based upon expression QTL data we collected in DO and CC mice and analyses using publicly available gene expression and phenotype databases. These findings may advance understanding of the genetics that drive impulsive behavior and enhance risk for substance use disorders. 2022-12 2022-11-04 /pmc/articles/PMC9879139/ /pubmed/36714272 http://dx.doi.org/10.1016/j.addicn.2022.100045 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) )
spellingShingle Article
Bagley, Jared R.
Bailey, Lauren S.
Gagnon, Leona H.
He, Hao
Philip, Vivek M.
Reinholdt, Laura G.
Tarantino, Lisa M.
Chesler, Elissa J.
Jentsch, James D.
Behavioral phenotypes revealed during reversal learning are linked with novel genetic loci in diversity outbred mice
title Behavioral phenotypes revealed during reversal learning are linked with novel genetic loci in diversity outbred mice
title_full Behavioral phenotypes revealed during reversal learning are linked with novel genetic loci in diversity outbred mice
title_fullStr Behavioral phenotypes revealed during reversal learning are linked with novel genetic loci in diversity outbred mice
title_full_unstemmed Behavioral phenotypes revealed during reversal learning are linked with novel genetic loci in diversity outbred mice
title_short Behavioral phenotypes revealed during reversal learning are linked with novel genetic loci in diversity outbred mice
title_sort behavioral phenotypes revealed during reversal learning are linked with novel genetic loci in diversity outbred mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9879139/
https://www.ncbi.nlm.nih.gov/pubmed/36714272
http://dx.doi.org/10.1016/j.addicn.2022.100045
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