ArticleProceedings of the National Academy of Sciences of the United States of America2016
Genetic background and epigenetic modifications in the core of the nucleus accumbens predict addiction-like behavior in a rat model.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Genetic Architecture of Addiction-Relevant Behaviors in Outbred Sprague-Dawley Rats Reveals Loci for Anxiety-Like and Nociceptive Traits.Genes, brain, and behavior · 2026Article
- Differential acquisition of cocaine and heroin self-administration in a rat model of internalizing versus externalizing temperament.bioRxiv : the preprint server for biology · 2026Article
- Genetic Architecture of Addiction-Relevant Behaviors in Outbred Sprague-Dawley Rats Reveals Loci for Anxiety-Like and Nociceptive Traits.bioRxiv : the preprint server for biology · 2026Article
- Nandrolone alters the behavioral response to cocaine as well as striatal and cortical dopamine receptors of prepubertal male rats.Scientific reports · 2025Article
- Bioenergetic-related gene expression in the hippocampus predicts internalizing vs. externalizing behavior in an animal model of temperament.Frontiers in molecular neuroscience · 2025Article
- Understanding the shift to compulsion in addiction: insights from personality traits, social factors, and neurobiology.Frontiers in psychology · 2024Review
- Listening to the Data: Computational Approaches to Addiction and Learning.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Review
- Early life adversity: Epigenetic regulation underlying drug addiction susceptibility.Molecular and cellular neurosciences · 2023Review
- Cell-type specific synaptic plasticity in dorsal striatum is associated with punishment-resistance compulsive-like cocaine self-administration in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Novelty-induced locomotor behavior predicts heroin addiction vulnerability in male, but not female, rats.Psychopharmacology · 2022Article
- Novelty preference does not predict trait cocaine behaviors in male rats.Addiction neuroscience · 2022Article
- Modeling heritability of temperamental differences, stress reactivity, and risk for anxiety and depression: Relevance to research domain criteria (RDoC).The European journal of neuroscience · 2022Review
- Noradrenergic circuits and signaling in substance use disorders.Neuropharmacology · 2022Review
- Investigating individual differences in opioid-taking and opioid-seeking behavior in male rats.Psychopharmacology · 2022Article
- Inhibition of a cortico-thalamic circuit attenuates cue-induced reinstatement of drug-seeking behavior in "relapse prone" male rats.Psychopharmacology · 2022Article
- Epigenetic Effects of Addictive Drugs in the Nucleus Accumbens.Frontiers in molecular neuroscience · 2022Review
- Adolescent cocaine differentially impacts psychomotor sensitization and epigenetic profiles in adult male rats with divergent affective phenotypes.Frontiers in 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
- Disruption of the PDZ domain-binding motif of the dopamine transporter uniquely alters nanoscale distribution, dopamine homeostasis, and reward motivation.The Journal of biological chemistry · 2021Article
- The sensation seeking trait confers a dormant susceptibility to addiction that is revealed by intermittent cocaine self-administration in rats.Neuropharmacology · 2021Article
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Authors and funding
9 authors.
Funding
Abstract
This study provides a demonstration in the rat of a clear genetic difference in the propensity for addiction-related behaviors following prolonged cocaine self-administration. It relies on the use of selectively bred high-responder (bHR) and low-responder (bLR) rat lines that differ in several characteristics associated with "temperament," including novelty-induced locomotion and impulsivity. We show that bHR rats exhibit behaviors reminiscent of human addiction, including persistent cocaine-seeking and increased reinstatement of cocaine seeking. To uncover potential underlying mechanisms of this differential vulnerability, we focused on the core of the nucleus accumbens and examined expression and epigenetic regulation of two transcripts previously implicated in bHR/bLR differences: fibroblast growth factor (FGF2) and the dopamine D2 receptor (D2). Relative to bHRs, bLRs had lower FGF2 mRNA levels and increased association of a repressive mark on histones (H3K9me3) at the FGF2 promoter. These differences were apparent under basal conditions and persisted even following prolonged cocaine self-administration. In contrast, bHRs had lower D2 mRNA under basal conditions, with greater association of H3K9me3 at the D2 promoter and these differences were no longer apparent following prolonged cocaine self-administration. Correlational analyses indicate that the association of H3K9me3 at D2 may be a critical substrate underlying the propensity to relapse. These findings suggest that low D2 mRNA levels in the nucleus accumbens core, likely mediated via epigenetic modifications, may render individuals more susceptible to cocaine addiction. In contrast, low FGF2 levels, which appear immutable even following prolonged cocaine exposure, may serve as a protective factor.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.