ArticleBiological psychiatry2018
E3 Ubiquitin-Protein Ligase SMURF1 in the Nucleus Accumbens Mediates Cocaine Seeking.
Article in Biological psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Changes in nucleus accumbens core translatome accompanying incubation of cocaine craving.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- An Epigenetic Mechanism Promoting Heroin Relapse After Prolonged Abstinence.Biological psychiatry · 2025Article
- A Novel Role for the Histone Demethylase JMJD3 in Mediating Heroin-Induced Relapse-Like Behaviors.Biological psychiatry · 2025Article
- Profiling gene alterations in striatonigral neurons associated with incubation of methamphetamine craving by cholera toxin subunit B-based fluorescence-activated cell sorting.Frontiers in cellular neuroscience · 2025Article
- Integrative Analysis of Morphine-Induced Differential Circular RNAs and ceRNA Networks in the Medial Prefrontal Cortex.Molecular neurobiology · 2024Article
- Research Progress in Function and Regulation of E3 Ubiquitin Ligase SMURF1.Current medical science · 2023Review
- Postpartum scarcity-adversity inflicts sex-specific cerebellar adaptations and reward behaviors in adolescence.Pharmacology, biochemistry, and behavior · 2023Article
- The ubiquitin-proteasome system and learning-dependent synaptic plasticity - A 10 year update.Neuroscience and biobehavioral reviews · 2023Review
- The roles of ubiquitin-proteasome system and regulator of G protein signaling 4 in behavioral sensitization induced by a single morphine exposure.Brain and behavior · 2023Article
- Neuroadaptations and TGF-β signaling: emerging role in models of neuropsychiatric disorders.Molecular psychiatry · 2022Review
- A role for the endocannabinoid enzymes monoacylglycerol and diacylglycerol lipases in cue-induced cocaine craving following prolonged abstinence.Addiction biology · 2021Article
- Neuroadaptations in the dorsal hippocampus underlie cocaine seeking during prolonged abstinence.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The diversity of linkage-specific polyubiquitin chains and their role in synaptic plasticity and memory formation.Neurobiology of learning and memory · 2020Review
- Sex-Specific Role for Egr3 in Nucleus Accumbens D2-Medium Spiny Neurons Following Long-Term Abstinence From Cocaine Self-administration.Biological psychiatry · 2020Article
- Ubiquitin-proteasomal regulation of chromatin remodeler INO80 in the nucleus accumbens mediates persistent cocaine craving.Science advances · 2019Article
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundSubstance use disorder is a neurobiological disease characterized by episodes of relapse despite periods of withdrawal. It is thought that neuroadaptations in discrete brain areas of the reward pathway, including the nucleus accumbens, underlie these aberrant behaviors. The ubiquitin-proteasome system degrades proteins and has been shown to be involved in cocaine-induced plasticity, but the role of E3 ubiquitin ligases, which conjugate ubiquitin to substrates, is unknown. Here, we examined E3 ubiquitin-protein ligase SMURF1 (SMURF1) in neuroadaptations and relapse behavior during withdrawal following cocaine self-administration.
methodsSMURF1 and downstream targets ras homolog gene family, member A (RhoA), SMAD1/5, and Runt-related transcript factor 2 were examined using Western blotting (n = 9-11/group), quantitative polymerase chain reaction (n = 6-9/group), co-immunoprecipitation (n = 9-11/group), tandem ubiquitin binding entities affinity purification (n = 5-6/group), and quantitative chromatin immunoprecipitation (n = 3-6/group) (2 rats/sample). Viral-mediated gene transfer (n = 7-12/group) and intra-accumbal microinjections (n = 9-10/group) were used to examine causal roles of SMURF1 and substrate RhoA, respectively, in cue-induced cocaine seeking.
resultsSMURF1 protein expression was decreased, while SMURF1 substrates RhoA and SMAD1/5 were increased, in the nucleus accumbens on withdrawal day 7, but not on withdrawal day 1, following cocaine self-administration. Viral-mediated gene transfer of Smurf1 or constitutive activation of RhoA attenuated cue-induced cocaine seeking, while catalytically inactive Smurf1 enhanced cocaine seeking. Furthermore, SMURF1-regulated, SMAD1/5-associated transcription factor Runt-related transcript factor 2 displayed increased binding at promoter regions of genes previously associated with cocaine-induced plasticity.
conclusionsSMURF1 is a key mediator of neuroadaptations in the nucleus accumbens following cocaine exposure and mediates cue-induced cocaine seeking during withdrawal.
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