ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Opposing role for Egr3 in nucleus accumbens cell subtypes in cocaine action.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 135 citations in OpenAlex.
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- Nrf2 Deficiency Exacerbates Methamphetamine-Induced Neuronal Apoptosis and Cognitive Dysfunction in Male Mice.International journal of molecular sciences · 2026Article
- NPAS3-regulated astrocyte mitochondrial bioenergetics is required for cognition.Science advances · 2026Article
- Transcription factors implicated in substance use disorder, from immediate early genes to altered gene expression.Brain research · 2026Review
- Article
- Disruption of Cell-Type-Specific Molecular Programs of Medium Spiny Neurons in Autism.bioRxiv : the preprint server for biology · 2025Article
- Prelimbic cortex to ventral tegmental area projection regulates early social isolation stress-potentiated heroin seeking in mice.Nature communications · 2025Article
- Translin deletion impairs cocaine-induced locomotor sensitization and RGS8 expression in the nucleus accumbens.Acta pharmacologica Sinica · 2025Article
- Dopamine Receptor 1 Specific CRISPRa Mice Exhibit Disrupted Behaviors and Striatal Baseline Cellular Activity.eNeuro · 2025Article
- Molecular and cellular rhythms in excitatory and inhibitory neurons in the mouse prefrontal cortex.Cerebral cortex (New York, N.Y. : 1991) · 2025Article
- Changes in nucleus accumbens core translatome accompanying incubation of cocaine craving.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Dopamine receptor 1 specific CRISPRa mice exhibit disrupted behaviors and striatal baseline cellular activity.bioRxiv : the preprint server for biology · 2025Article
- Cocaine-induced gene regulation in D1 and D2 neuronal ensembles of the nucleus accumbens.Communications biology · 2025Article
- The single-cell opioid responses in the context of HIV (SCORCH) consortium.Molecular psychiatry · 2024Article
- Cell type-specific epigenetic priming of gene expression in nucleus accumbens by cocaine.Science advances · 2024Article
- Elucidating the molecular symphony: unweaving the transcriptional & epigenetic pathways underlying neuroplasticity in opioid dependence and withdrawal.Psychopharmacology · 2024Review
- Treadmill exercise training inhibits morphine CPP by reversing morphine effects on GABA neurotransmission in D2-MSNs of the accumbens-pallidal pathway in male mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Cell-type and sex-specific rhythmic gene expression in the nucleus accumbens.Molecular psychiatry · 2024Article
- SIRT1 Coordinates Transcriptional Regulation of Neural Activity and Modulates Depression-Like Behaviors in the Nucleus Accumbens.Biological psychiatry · 2024Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
An imbalance in molecular signaling cascades and transcriptional regulation in nucleus accumbens (NAc) medium spiny neuron (MSN) subtypes, those enriched in dopamine D1 versus D2 receptors, is implicated in the behavioral responses to psychostimulants. To provide further insight into the molecular mechanisms occurring in MSN subtypes by cocaine, we examined the transcription factor early growth response 3 (Egr3). We evaluated Egr3 because it is a target of critical cocaine-mediated signaling pathways and because Egr3-binding sites are found on promoters of key cocaine-associated molecules. We first used a RiboTag approach to obtain ribosome-associated transcriptomes from each MSN subtype and found that repeated cocaine administration induced Egr3 ribosome-associated mRNA in NAc D1-MSNs while reducing Egr3 in D2-MSNs. Using Cre-inducible adeno-associated viruses combined with D1-Cre and D2-Cre mouse lines, we observed that Egr3 overexpression in D1-MSNs enhances rewarding and locomotor responses to cocaine, whereas overexpression in D2-MSNs blunts these behaviors. miRNA knock-down of Egr3 in MSN subtypes produced opposite behavioral responses from those observed with overexpression. Finally, we found that repeated cocaine administration altered Egr3 binding to promoters of genes that are important for cocaine-mediated cellular and behavioral plasticity. Genes with increased Egr3 binding to promoters, Camk2α, CREB, FosB, Nr4a2, and Sirt1, displayed increased mRNA in D1-MSNs and, in some cases, a reduction in D2-MSNs. Histone and the DNA methylation enzymes G9a and Dnmt3a displayed reduced Egr3 binding to their promoters and reduced mRNA in D1-MSNs. Our study provides novel insight into an opposing role of Egr3 in select NAc MSN subtypes in cocaine action.
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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 OpenQuestion graph.