ArticleProceedings of the National Academy of Sciences of the United States of America2019
Exploratory locomotion, a predictor of addiction vulnerability, is oligogenic in rats selected for this phenotype.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Genetic Liability for Internalizing Versus Externalizing Behavior Manifests in the Developing and Adult Hippocampus: Insight From a Meta-analysis of Transcriptional Profiling Studies in a Selectively Bred Rat Model.Biological psychiatry · 2021Pooled it
- Large-scale behavioral characterization of oxycodone self-administration in heterogeneous stock rats reveals initial analgesic effects are associated with addiction-like behaviors.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Charting the Unknown : Sex Differences in Spatial Exploration Across the Lifespan.Human nature (Hawthorne, N.Y.) · 2025Article
- Bioenergetic-related gene expression in the hippocampus predicts internalizing vs. externalizing behavior in an animal model of temperament.Frontiers in molecular neuroscience · 2025Article
- Adolescent environmental enrichment induces social resilience and alters neural gene expression in a selectively bred rodent model with anxious phenotype.Neurobiology of stress · 2024Article
- Adolescent environmental enrichment induces social resilience and alters neural gene expression in a selectively bred rodent model with anxious phenotype.bioRxiv : the preprint server for biology · 2024Article
- FABEL: Forecasting Animal Behavioral Events with Deep Learning-Based Computer Vision.bioRxiv : the preprint server for biology · 2024Article
- An ethogram analysis of cutaneous thermal pain sensitivity and oxycodone reward-related behaviors in rats.Scientific reports · 2023Article
- Transcriptome-wide gene-gene interaction associations elucidate pathways and functional enrichment of complex traits.PLoS genetics · 2023Article
- An ethogram analysis of cutaneous thermal pain sensitivity and oxycodone reward-related behaviors in rats.Research square · 2023Article
- From Phenomes to Genes: Phenotype-based Strategies in Rodents for Research on the Neurobiological and Genetic Bases of Psychiatric-relevant Traits.Current neuropharmacology · 2023Article
- Astrocyte Molecular Clock Function in the Nucleus Accumbens Is Important for Reward-Related Behavior.Biological psychiatry · 2022Article
- GeneCup: mining PubMed and GWAS catalog for gene-keyword relationships.G3 (Bethesda, Md.) · 2022Article
- Molecular rhythm alterations in prefrontal cortex and nucleus accumbens associated with opioid use disorder.Translational psychiatry · 2022Article
- Differences in microglia morphological profiles reflect divergent emotional temperaments: insights from a selective breeding model.Translational psychiatry · 2022Article
- Genome-wide association study in a rat model of temperament identifies multiple loci for exploratory locomotion and anxiety-like traits.Frontiers in genetics · 2022Article
- Common Factors Underlying Diverse Responses in Alcohol Use Disorder.Psychiatric research and clinical practice · 2021Article
- Whole-Genome Sequencing of Inbred Mouse Strains Selected for High and Low Open-Field Activity.Behavior genetics · 2021Article
- A Novel Assay Allowing Drug Self-Administration, Extinction, and Reinstatement Testing in Head-Restrained Mice.Frontiers in behavioral neuroscience · 2021Article
- Turning strains into strengths for understanding psychiatric disorders.Molecular psychiatry · 2020Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Artificially selected model organisms can reveal hidden features of the genetic architecture of the complex disorders that they model. Addictions are disease phenotypes caused by different intermediate phenotypes and pathways and thereby are potentially highly polygenic. High responder (bHR) and low responder (bLR) rat lines have been selectively bred (b) for exploratory locomotion (EL), a behavioral phenotype correlated with novelty-seeking, impulsive response to reward, and vulnerability to addiction, and is inversely correlated with spontaneous anxiety and depression-like behaviors. The rapid response to selection indicates loci of large effect for EL. Using exome sequencing of HR and LR rats, we identified alleles in gene-coding regions that segregate between the two lines. Quantitative trait locus (QTL) analysis in F2 rats derived from a bHR × bLR intercross confirmed that these regions harbored genes affecting EL. The combined effects of the seven genome-wide significant QTLs accounted for approximately one-third of the total variance in EL, and two-thirds of the variance attributable to genetic factors, consistent with an oligogenic architecture of EL estimated both from the phenotypic distribution of F2 animals and rapid response to selection. Genetic association in humans linked
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