Genetic Loci Influencing Cue‐Reactivity in Heterogeneous Stock Rats DOI Creative Commons
Christopher P. King, Apurva S. Chitre, Joel D. Leal‐Gutiérrez

et al.

Genes Brain & Behavior, Journal Year: 2025, Volume and Issue: 24(2)

Published: March 6, 2025

Addiction vulnerability is associated with the tendency to attribute incentive salience reward predictive cues. Both addiction and attribution of are influenced by environmental genetic factors. To characterize contributions attribution, we performed a genome-wide association study (GWAS) in cohort 1596 heterogeneous stock (HS) rats. Rats underwent Pavlovian conditioned approach task that characterized responses food-associated stimuli ("cues"). Responses ranged from cue-directed "sign-tracking" behavior food-cup directed "goal-tracking" (12 measures, SNP heritability: 0.051-0.215). Next, rats novel operant for unrewarded presentations cue using reinforcement procedure. GWAS identified 14 quantitative trait loci (QTLs) 11 12 traits across both tasks. Interval sizes these QTLs varied widely. Seven shared QTL on chromosome 1 contained few genes (e.g., Tenm4, Mir708) have been substance use disorders other psychiatric humans. Other candidate Wnt11, Pak1) this region had coding variants expression-QTLs mesocorticolimbic regions brain. We also conducted Phenome-Wide Association Study (PheWAS) addiction-related behaviors HS found was nicotine self-administration separate These results provide starting point molecular dissection motivational processes further support relationship between drug abuse-related traits.

Language: Английский

Genetic Loci Influencing Cue‐Reactivity in Heterogeneous Stock Rats DOI Creative Commons
Christopher P. King, Apurva S. Chitre, Joel D. Leal‐Gutiérrez

et al.

Genes Brain & Behavior, Journal Year: 2025, Volume and Issue: 24(2)

Published: March 6, 2025

Addiction vulnerability is associated with the tendency to attribute incentive salience reward predictive cues. Both addiction and attribution of are influenced by environmental genetic factors. To characterize contributions attribution, we performed a genome-wide association study (GWAS) in cohort 1596 heterogeneous stock (HS) rats. Rats underwent Pavlovian conditioned approach task that characterized responses food-associated stimuli ("cues"). Responses ranged from cue-directed "sign-tracking" behavior food-cup directed "goal-tracking" (12 measures, SNP heritability: 0.051-0.215). Next, rats novel operant for unrewarded presentations cue using reinforcement procedure. GWAS identified 14 quantitative trait loci (QTLs) 11 12 traits across both tasks. Interval sizes these QTLs varied widely. Seven shared QTL on chromosome 1 contained few genes (e.g., Tenm4, Mir708) have been substance use disorders other psychiatric humans. Other candidate Wnt11, Pak1) this region had coding variants expression-QTLs mesocorticolimbic regions brain. We also conducted Phenome-Wide Association Study (PheWAS) addiction-related behaviors HS found was nicotine self-administration separate These results provide starting point molecular dissection motivational processes further support relationship between drug abuse-related traits.

Language: Английский

Citations

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