ArticleBiological psychiatry2019
Extracellular Matrix Signaling Through β3 Integrin Mediates Cocaine Cue-Induced Transient Synaptic Plasticity and Relapse.
Article in Biological psychiatry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
- Cannabinoid use generalizes stress responses: involvement of astrocyte plasticity and activation of matrix metalloproteinases in the nucleus accumbens core.Molecular psychiatry · 2026Article
- Cannabidiol Attenuates Heroin Seeking in Male Rats Associated With Normalization of Discrete Neurobiological Signatures Within the Nucleus Accumbens With Subregional Specificity.Biological psychiatry · 2026Article
- Human Stem Cell-Derived Neurospheroids and a Multi-Assay Strategy Provide Brain Cytotoxicity New Insights from ADB-FUBIATA Exposure.Neurotoxicity research · 2026Article
- Prelimbic cortex layer 5 GABAergic neurons mediate chronic pain and memory impairment by regulating excitatory/inhibitory imbalance.The journal of headache and pain · 2026Article
- Independent Heritability of Aversive Learning Influences on Cocaine-Seeking and Punishment Resistance in Rats.eNeuro · 2026Article
- Article
- Astrocytes Control Cocaine-Induced Synaptic Plasticity and Reward Through the Matricellular Protein Hevin.Biological psychiatry · 2025Article
- Transcriptional characterization of cocaine withdrawal versus extinction within nucleus accumbens in male rats.Nature communications · 2025Article
- Dopamine DNeuroscience letters · 2025Article
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- The Perineuronal Net Protein Brevican Acts in Nucleus Accumbens Parvalbumin-Expressing Interneurons of Adult Mice to Regulate Excitatory Synaptic Inputs and Motivated Behaviors.Biological psychiatry · 2024Article
- Perineuronal Nets in the Rat Medial Prefrontal Cortex Alter Hippocampal-Prefrontal Oscillations and Reshape Cocaine Self-Administration Memories.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Formation of an Enduring Ensemble of Accumbens Neurons Leads to Prepotent Seeking for Cocaine Over Natural Reward Cues.bioRxiv : the preprint server for biology · 2024Article
- ΔAddiction biology · 2023Article
- Three-Dimensional Cell Cultures: The Bridge between In Vitro and In Vivo Models.International journal of molecular sciences · 2023Review
- Intrusive thinking: Circuit and synaptic mechanisms of a transdiagnostic psychiatric symptom.Neuroscience and biobehavioral reviews · 2023Review
- Matrix metalloproteinase activity during methamphetamine cued relapse.Addiction biology · 2023Article
- Dynamic regulation of the extracellular matrix in reward memory processes: a question of time.Frontiers in cellular neuroscience · 2023Review
- Astrocytes in the ventral pallidum extinguish heroin seeking through GAT-3 upregulation and morphological plasticity at D1-MSN terminals.Molecular psychiatry · 2022Article
- Editorial: Brain extracellular matrix: Involvement in adult neural functions and disease volume II.Frontiers in integrative neuroscience · 2022Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCue-induced relapse to drug use is a primary symptom of cocaine addiction. Cue-induced transient excitatory synaptic potentiation (t-SP) induced in the nucleus accumbens mediates cued cocaine seeking in rat models of relapse. Cue-induced t-SP depends on extracellular signaling by matrix metalloproteases (MMPs), but it is unknown how this catalytic activity communicates with nucleus accumbens neurons to induce t-SP and cocaine seeking.
methodsMale Sprague Dawley rats (N = 125) were trained to self-administer cocaine, after which self-administration was extinguished and then reinstated by cocaine-conditioned cues. We used a morpholino antisense strategy to knock down the β1 or β3 integrin subunits or inhibitors to prevent phosphorylation of the integrin signaling kinases focal adhesion kinase (FAK) or integrin-linked kinase. We quantified protein changes with immunoblotting and t-SP by measuring dendritic spine morphology and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid/N-methyl-D-aspartate glutamate currents. Integrin signaling was stimulated by microinjecting an MMP activator or integrin peptide ligand into the accumbens.
resultsKnockdown of β3 integrin or FAK inhibitor, but not β1 integrin or integrin-linked kinase inhibitor, prevented cue-induced cocaine seeking but not sucrose seeking. β3 integrin knockdown prevented t-SP as measured by preventing the cue-induced increases in both alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid/N-methyl-D-aspartate glutamate ratio and spine head diameter. Activating MMP gelatinases with tissue plasminogen activator potentiated cue-induced reinstatement, which was prevented by β3 integrin knockdown and FAK inhibition. Stimulating integrin receptors with the RGD ligand liberated by MMP gelatinase activity also potentiated cued cocaine seeking.
conclusionsActivation of MMP gelatinase in the extracellular space is necessary for and potentiates cued cocaine seeking. This extracellular catalysis stimulates β3 integrins and activates FAK to induce t-SP and promote cue-induced cocaine seeking.
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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.