ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2021
Restoring glutamate homeostasis in the nucleus accumbens via endocannabinoid-mimetic drug prevents relapse to cocaine seeking behavior in rats.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- The neuroimmune-glutamate hypothesis of addiction.Neuroscience and biobehavioral reviews · 2026Review
- Pigment Epithelium-Derived Factor Deficiency Impairs Hippocampal Glutamate Homeostasis and Cognitive Function by Downregulating Astrocytic GLT-1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Sex-specific role of the 5-HTNature communications · 2025Article
- The mGlu5 receptor negative allosteric modulator mavoglurant reduces escalated cocaine self-administration in male and female rats.Psychopharmacology · 2024Article
- Fatty acid binding protein 7 plays an important modulatory sex-dependent role on brain endocannabinoid levels and THC metabolism.PloS one · 2024Article
- Astrocyte-Neuron Interactions in Substance Use Disorders.Advances in neurobiology · 2024Review
- Beyond the 5-HTThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Review
- Role of mesolimbic cannabinoid receptor 1 in stress-driven increases in cocaine self-administration in male rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Identification of a novel fatty acid binding protein-5-CB2 receptor-dependent mechanism regulating anxiety behaviors in the prefrontal cortex.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Fatty Acid-Binding Protein 5 Gene Deletion Enhances Nicotine-Conditioned Place Preference: Illuminating the Putative Gateway Mechanisms.Future pharmacology · 2023Article
- Article
- An orbitofrontal cortex-anterior insular cortex circuit gates compulsive cocaine use.Science advances · 2022Article
- Regulation of glutamate homeostasis in the nucleus accumbens by astrocytic CB1 receptors and its role in cocaine-motivated behaviors.Addiction neuroscience · 2022Article
- Astrocytes: the neglected stars in the central nervous system and drug addiction.Medical review (2021) · 2022Review
- Early-life adversity increases anxiety-like behavior and modifies synaptic protein expression in a region-specific manner.Frontiers in behavioral neuroscience · 2022Article
- Cocaine experience induces functional adaptations in astrocytes: Implications for synaptic plasticity in the nucleus accumbens shell.Addiction biology · 2021Article
- CB1R activation in nucleus accumbens core promotes stress-induced reinstatement of cocaine seeking by elevating extracellular glutamate in a drug-paired context.Scientific reports · 2021Article
- Neuroprotective and Immunomodulatory Action of the Endocannabinoid System under Neuroinflammation.International journal of molecular sciences · 2021Review
- Melatonin Blocks Morphine-Induced Place Preference: Involvement of GLT-1, NF-κB, BDNF, and CREB in the Nucleus Accumbens.Frontiers in behavioral neuroscience · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Impaired glutamate homeostasis is a key characteristic of the neurobiology of drug addiction in rodent models and contributes to the vulnerability to relapse to drug seeking. Although disrupted astrocytic and presynaptic regulation of glutamate release has been considered to constitute with impaired glutamate homeostasis in rodent model of drug relapse, the involvement of endocannabinoids (eCBs) in this neurobiological process has remained largely unknown. Here, using cocaine self-administration in rats, we investigated the role of endocannabinoids in impaired glutamate homeostasis in the core of nucleus accumbens (NAcore), which was indicated by augmentation of spontaneous synaptic glutamate release, downregulation of metabotropic glutamate receptor 2/3 (mGluR2/3), and mGluR5-mediated astrocytic glutamate release. We found that the endocannabinoid, anandamide (AEA), rather than 2-arachidonoylglycerol elicited glutamate release through presynaptic transient receptor potential vanilloid 1 (TRPV1) and astrocytic cannabinoid type-1 receptors (CB1Rs) in the NAcore of saline-yoked rats. In rats with a history of cocaine self-administration and extinction training, AEA failed to alter synaptic glutamate release in the NAcore, whereas CB1R-mediated astrocytic glutamate release by AEA remained functional. In order to induce increased astrocytic glutamate release via exogenous AEA, (R)-methanandamide (methAEA, a metabolically stable form of AEA) was chronically infused in the NAcore via osmotic pumps during extinction training. Restoration of mGluR2/3 function and mGluR5-mediated astrocytic glutamate release was observed after chronic methAEA infusion. Additionally, priming or cue-induced reinstatement of cocaine seeking was inhibited in methAEA-infused rats. These results demonstrate that enhancing endocannabinoid signaling is a potential pathway to restore glutamate homeostasis and may represent a promising therapeutic strategy for preventing cocaine relapse.
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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.