ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2018
Overexpression of the Histone Dimethyltransferase G9a in Nucleus Accumbens Shell Increases Cocaine Self-Administration, Stress-Induced Reinstatement, and Anxiety.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed.
- G9a inhibition reduces stress-potentiated alcohol drinking in both male and female mice: Implications for safe and effective pharmacological therapeutics for alcohol use disorder.Alcohol, clinical & experimental research · 2026Article
- Addictive drug abuse and depression-a focus on epigenetics.Communications biology · 2026Review
- Targeting G9a decreases escalated alcohol drinking in male mice in a model of combined stress and chronic alcohol exposure.Alcohol, clinical & experimental research · 2025Article
- Auditory cortical neurons are recruited to encode fear signals and anxiety by neuroligin-3-mediated synapse formation.Translational psychiatry · 2025Article
- Cocaine perturbs neurodevelopment and increases neuroinflammation in a prenatal cerebral organoid model.Translational psychiatry · 2025Article
- The Histone Lysine Demethylase KDM7A Contributes to Reward Memory via Fscn1-Induced Synaptic Plasticity in the Medial Prefrontal Cortex.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Associative memory cells of encoding fear signals and anxiety are recruited by neuroligin-3-mediated synapse formation.Communications biology · 2024Article
- Histone Methyltransferase G9a Plays an Essential Role on Nicotine Preference in Zebrafish.Molecular neurobiology · 2024Article
- Chronic alcohol-induced long-lasting working memory deficits are associated with altered histone H3K9 dimethylation in the prefrontal cortex.Frontiers in behavioral neuroscience · 2024Article
- Epigenetics of Fear, Anxiety and Stress - Focus on Histone Modifications.Current neuropharmacology · 2024Article
- How life events may confer vulnerability to addiction: the role of epigenetics.Frontiers in molecular neuroscience · 2024Review
- Article
- IGF-1 Microinjection in the Prefrontal Cortex Attenuates Fentanyl-Seeking Behavior in Mice.The international journal of neuropsychopharmacology · 2023Article
- Formation and fate of an engram in the lateral amygdala supporting a rewarding memory in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review.eNeuro · 2023Review
- Epac2 in midbrain dopamine neurons contributes to cocaine reinforcement via enhancement of dopamine release.eLife · 2022Article
- Brain systems in cocaine abstinence-induced anxiety-like behavior in rodents: A review.Addiction neuroscience · 2022Article
- Epigenetic Effects of Addictive Drugs in the Nucleus Accumbens.Frontiers in molecular neuroscience · 2022Review
- The histone methyltransferase G9a mediates stress-regulated alcohol drinking.Addiction biology · 2022Article
- Key transcription factors mediating cocaine-induced plasticity in the nucleus accumbens.Molecular psychiatry · 2022Review
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Authors and funding
7 authors.
Funding
Abstract
Repeated exposure to cocaine induces lasting epigenetic changes in neurons that promote the development and persistence of addiction. One epigenetic alteration involves reductions in levels of the histone dimethyltransferase G9a in nucleus accumbens (NAc) after chronic cocaine administration. This reduction in G9a may enhance cocaine reward because overexpressing G9a in the NAc decreases cocaine-conditioned place preference. Therefore, we hypothesized that HSV-mediated G9a overexpression in the NAc shell (NAcSh) would attenuate cocaine self-administration (SA) and cocaine-seeking behavior. Instead, we found that G9a overexpression, and the resulting increase in histone 3 lysine 9 dimethylation (H3K9me2), increases sensitivity to cocaine reinforcement and enhances motivation for cocaine in self-administering male rats. Moreover, when G9a overexpression is limited to the initial 15 d of cocaine SA training, it produces an enduring postexpression enhancement in cocaine SA and prolonged (over 5 weeks) increases in reinstatement of cocaine seeking induced by foot-shock stress, but in the absence of continued global elevations in H3K9me2. The increase in stress-induced reinstatement is paralleled by heightened anxiety measures, suggesting that countering the cocaine-induced decreases in endogenous G9a with ectopic G9a overexpression leads to lasting anxiogenic effects. Finally, we found an enduring reduction in phosphorylated cAMP-response element binding protein levels in the NAcSh that could account for the increased anxiety. These data demonstrate a novel role for G9a in promoting comorbid cocaine addiction and anxiety and suggest that increased epigenetic repression of transcription through H3K9 during cocaine use can have long-lasting and unexpected negative consequences on behavior.
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