{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T20:54:52Z","timestamp":1781211292936,"version":"3.54.1"},"posted":{"date-parts":[[2024,3,18]]},"group-title":"Neuroscience","reference-count":115,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,4,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  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 (\u201ccues\u201d). Rats exhibited either cue-directed \u201csign-tracking\u201d behavior or food-cup directed \u201cgoal-tracking\u201d 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,\n                  <jats:italic>\n                    h\n                    <jats:sup>2<\/jats:sup>\n                  <\/jats:italic>\n                  = .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 (\n                  <jats:italic>e.g. Tenm4<\/jats:italic>\n                  ,\n                  <jats:italic>Mir708<\/jats:italic>\n                  ) that have been associated with substance use disorders and other mental health traits in humans. Other candidate genes (\n                  <jats:italic>e.g. Wnt11, Pak1<\/jats:italic>\n                  ) 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.\n                <\/jats:p>","DOI":"10.1101\/2024.03.13.584852","type":"posted-content","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T15:30:13Z","timestamp":1710775813000},"source":"Crossref","is-referenced-by-count":4,"title":["Genomic Loci Influencing Cue-Reactivity in Heterogeneous Stock Rats"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6641-237X","authenticated-orcid":false,"given":"Christopher P.","family":"King","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apurva S.","family":"Chitre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel 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