Genomic Loci Influencing Cue-Reactivity in Heterogeneous Stock Rats.

Autor: King CP; Department of Psychology, University at Buffalo, Buffalo, USA.; Clinical and Research Institute on Addictions, Buffalo, USA., Chitre AS; Department of Psychiatry, University of California San Diego, La Jolla, USA., Leal-Gutiérrez JD; Department of Psychiatry, University of California San Diego, La Jolla, USA., Tripi JA; Department of Psychology, University at Buffalo, Buffalo, USA., Hughson AR; Department of Psychology, University of Michigan, Ann Arbor, USA., Horvath AP; Department of Psychology, University of Michigan, Ann Arbor, USA., Lamparelli AC; Department of Psychology, University at Buffalo, Buffalo, USA., George A; Clinical and Research Institute on Addictions, Buffalo, USA., Martin C; Clinical and Research Institute on Addictions, Buffalo, USA., Pierre CLS; Department of Genetics, Washington University Saint Louis, St. Louis, USA., Sanches T; Department of Psychiatry, University of California San Diego, La Jolla, USA., Bimschleger HV; Department of Psychiatry, University of California San Diego, La Jolla, USA., Gao J; Department of Psychiatry, University of California San Diego, La Jolla, USA., Cheng R; Department of Psychiatry, University of California San Diego, La Jolla, USA., Nguyen KM; Department of Psychiatry, University of California San Diego, La Jolla, USA., Holl KL; Department of Physiology, Medical College of Wisconsin, Milwaukee, USA., Polesskaya O; Department of Psychiatry, University of California San Diego, La Jolla, USA., Ishiwari K; Clinical and Research Institute on Addictions, Buffalo, USA.; Department of Pharmacology and Toxicology, University at Buffalo, Buffalo USA., Chen H; Department of Pharmacology, Addiction Science and Toxicology, University of Tennessee Health Science Center, Memphis, USA., Woods LCS; Department of Internal Medicine, Molecular Medicine, Center on Diabetes, Obesity and Metabolism, Wake Forest School of Medicine, Winston-Salem, USA., Palmer AA; Department of Psychiatry, University of California San Diego, La Jolla, USA.; Institute for Genomic Medicine, University of California San Diego, La Jolla, USA., Robinson TE; Department of Psychology, University of Michigan, Ann Arbor, USA., Flagel SB; Department of Psychiatry, University of Michigan, Ann Arbor, USA.; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, USA., Meyer PJ; Department of Psychology, University at Buffalo, Buffalo, USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 Apr 03. Date of Electronic Publication: 2024 Apr 03.
DOI: 10.1101/2024.03.13.584852
Abstrakt: Addiction vulnerability is associated with the tendency to attribute incentive salience to reward predictive cues; both addiction and the attribution of incentive salience are influenced by environmental and genetic factors. To characterize the genetic contributions to incentive salience attribution, we performed a genome-wide association study (GWAS) in a cohort of 1,645 genetically diverse heterogeneous stock (HS) rats. We tested HS rats in a Pavlovian conditioned approach task, in which we characterized the individual responses to food-associated stimuli ("cues"). Rats exhibited either cue-directed "sign-tracking" behavior or food-cup directed "goal-tracking" behavior. We then used the conditioned reinforcement procedure to determine whether rats would perform a novel operant response for unrewarded presentations of the cue. We found that these measures were moderately heritable (SNP heritability, h 2 = .189-.215). GWAS identified 14 quantitative trait loci (QTLs) for 11 of the 12 traits we examined. Interval sizes of these QTLs varied widely. 7 traits shared a QTL on chromosome 1 that contained a few genes ( e.g. Tenm4, Mir708 ) that have been associated with substance use disorders and other mental health traits in humans. Other candidate genes ( e.g. Wnt11, Pak1 ) in this region had coding variants and expression-QTLs in mesocorticolimbic regions of the brain. We also conducted a Phenome-Wide Association Study (PheWAS) on other behavioral measures in HS rats and found that regions containing QTLs on chromosome 1 were also associated with nicotine self-administration in a separate cohort of HS rats. These results provide a starting point for the molecular genetic dissection of incentive salience and provide further support for a relationship between attribution of incentive salience and drug abuse-related traits.
Databáze: MEDLINE