ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2019
Synaptic Microtubule-Associated Protein EB3 and SRC Phosphorylation Mediate Structural and Behavioral Adaptations During Withdrawal From Cocaine Self-Administration.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- E2F3a transcription factor mediates behavioral, cellular, and DNA-protein regulation of cocaine reward in the nucleus accumbens.Molecular psychiatry · 2026Article
- Hypocretin receptor 1 blockade early in abstinence prevents incubation of cocaine seeking and normalizes dopamine transmission.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Transcriptional characterization of cocaine withdrawal versus extinction within nucleus accumbens in male rats.Nature communications · 2025Article
- Neurobiology of the incubation of drug craving: An update.Pharmacological reviews · 2025Review
- The biology of addiction.Science signaling · 2025Review
- Schild Analysis of the Interaction between Parthenolide and Cocaine Suggests an Allosteric Relationship for Their Effects on Planarian Motility.Biomolecules · 2024Article
- Sex-Specific ADNP/NAP (Davunetide) Regulation of Cocaine-Induced Plasticity.Journal of molecular neuroscience : MN · 2024Article
- Circuit-Wide Gene Network Analysis Reveals Sex-Specific Roles for Phosphodiesterase 1b in Cocaine Addiction.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Targeting the cytoskeleton as a therapeutic approach to substance use disorders.Pharmacological research · 2024Review
- Single-nucleus genomics in outbred rats with divergent cocaine addiction-like behaviors reveals changes in amygdala GABAergic inhibition.Nature neuroscience · 2023Article
- Article
- Temperature- and chemical-induced neurotoxicity in zebrafish.Frontiers in physiology · 2023Review
- Metabolites of Cannabis Induce Cardiac Toxicity and Morphological Alterations in Cardiac Myocytes.International journal of molecular sciences · 2022Article
- Initial Evaluations of the Microtubule-Based PET Radiotracer, [Frontiers in medicine · 2022Article
- Proteomic Analysis Unveils Expressional Changes in Cytoskeleton- and Synaptic Plasticity-Associated Proteins in Rat Brain Six Months after Withdrawal from Morphine.Life (Basel, Switzerland) · 2021Article
- Understanding Emotions: Origins and Roles of the Amygdala.Biomolecules · 2021Review
- Effect of ethanol and cocaine on [Molecular biology reports · 2021Article
- Cocaine Induces Cytoskeletal Changes in Cardiac Myocytes: Implications for Cardiac Morphology.International journal of molecular sciences · 2021Article
- The p140Cap adaptor protein as a molecular hub to block cancer aggressiveness.Cellular and molecular life sciences : CMLS · 2021Review
- 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
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
Abstract
Addictive behaviors, including relapse, are thought to depend in part on long-lasting drug-induced adaptations in dendritic spine signaling and morphology in the nucleus accumbens (NAc). While the influence of activity-dependent actin remodeling in these phenomena has been studied extensively, the role of microtubules and associated proteins remains poorly understood. We report that pharmacological inhibition of microtubule polymerization in the NAc inhibited locomotor sensitization to cocaine and contextual reward learning. We then investigated the roles of microtubule end-binding protein 3 (EB3) and SRC kinase in the neuronal and behavioral responses to volitionally administered cocaine. In synaptoneurosomal fractions from the NAc of self-administering male rats, the phosphorylation of SRC at an activating site was induced after 1 d of withdrawal, while EB3 levels were increased only after 30 d of withdrawal. Blocking SRC phosphorylation during early withdrawal by virally overexpressing SRCIN1, a negative regulator of SRC activity known to interact with EB3, abolished the incubation of cocaine craving in both male and female rats. Conversely, mimicking the EB3 increase observed after prolonged withdrawal increased the motivation to consume cocaine in male rats. In mice, the overexpression of either EB3 or SRCIN1 increased dendritic spine density and altered the spine morphology of NAc medium spiny neurons. Finally, a cocaine challenge after prolonged withdrawal recapitulated most of the synaptic protein expression profiles observed at early withdrawal. These findings suggest that microtubule-associated signaling proteins such as EB3 cooperate with actin remodeling pathways, notably SRC kinase activity, to establish and maintain long-lasting cellular and behavioral alterations following cocaine self-administration.
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