Divergent risky decision-making and impulsivity behaviors in Lewis rat substrains with low genetic difference. Behav Neurosci 2023 Aug;137(4):254-267
Date
04/27/2023Pubmed ID
37104777Pubmed Central ID
PMC10524952DOI
10.1037/bne0000557Scopus ID
2-s2.0-85158841983 (requires institutional sign-in at Scopus site)Abstract
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).
Author List
Gabriel DBK, Liley AE, Franks HT, Minnes GL, Tutaj M, Dwinell MR, de Jong TV, Williams RW, Mulligan MK, Chen H, Simon NWAuthors
Melinda R. Dwinell PhD Professor in the Physiology department at Medical College of WisconsinMonika Tutaj Research Scientist II in the Physiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBehavior, Addictive
Decision Making
Female
Impulsive Behavior
Male
Rats
Rats, Inbred Lew
Risk-Taking
Substance-Related Disorders
