ArticleAddiction biology2020
Accumbens neuroimmune signaling and dysregulation of astrocytic glutamate transport underlie conditioned nicotine-seeking behavior.
Article in Addiction biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 54 citations in OpenAlex.
- Clavulanic acid is associated with moderation of cigarette use in patients with cocaine use disorder: A post-hoc analysis.Drug and alcohol dependence · 2026Trial
- An evaluation of N-acetylcysteine in a sequential oxycodone and cocaine rat self-administration model.Experimental and clinical psychopharmacology · 2026Article
- The neuroimmune-glutamate hypothesis of addiction.Neuroscience and biobehavioral reviews · 2026Review
- Nicotine self-administration suppresses both pro- and anti-inflammatory accumbens cytokines but does not induce apoptosis in female rats.Addiction neuroscience · 2026Article
- Utility of the Recombinase Driver CX3CR1-ERT2 Rat Strain in Nicotine Self-Administration.Cells · 2026Article
- MC-100093, a synthetic beta-lactam compound, and ceftriaxone modulate nicotine consumption, neuroinflammation and glutamatergic transporters in a nicotine self-administration mouse model.Psychopharmacology · 2026Article
- A single extinction-based treatment with N-Acetylcysteine produces long-term reduction in cocaine relapse.Translational psychiatry · 2026Article
- Neuroprotective effects of naringenin on nicotine-induced anxiety and depression: Involvement of monoaminergic systems, oxidative stress, and neuroinflammation on male rats.Current research in pharmacology and drug discovery · 2026Article
- From Stress to Substance Use Disorders: The Expanding Role of Microglia-Astrocyte Crosstalk in Neuroimmune and Glutamate Alterations in the Nucleus Accumbens.International journal of molecular sciences · 2025Review
- Glutamine synthetase in astrocytes of the caudate and putamen is responsible for locomotor sensitization after nicotine exposure.Acta pharmaceutica Sinica. B · 2025Article
- Dissociating the incubation of appetitive and consummatory behavior in a model of oral cocaine self-administration.Pharmacology, biochemistry, and behavior · 2025Article
- Investigating cocaine- and abstinence-induced effects on astrocyte gene expression in the nucleus accumbens.bioRxiv : the preprint server for biology · 2025Article
- Dissociating the incubation of appetitive and consummatory behavior in a model of oral cocaine self-administration.bioRxiv : the preprint server for biology · 2025Article
- Article
- Nicotine is an Immunosuppressant: Implications for Women's Health and Disease.Journal of neuroimmunology · 2024Review
- Fluorocitrate inhibition of astrocytes reduces nicotine self-administration and alters extracellular levels of glutamate and dopamine within the nucleus accumbens in male wistar rats.Neuropharmacology · 2024Article
- Something to talk about; crosstalk disruption at the neurovascular unit during HIV infection of the CNS.NeuroImmune pharmacology and therapeutics · 2024Article
- Astrocytic transcriptional and epigenetic mechanisms of drug addiction.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Astrocyte-Neuron Interactions in Substance Use Disorders.Advances in neurobiology · 2024Review
- Oxycodone withdrawal is associated with increased cocaine self-administration and aberrant accumbens glutamate plasticity in rats.Neuropharmacology · 2024Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Nicotine self-administration is associated with decreased expression of the glial glutamate transporter (GLT-1) and the cystine-glutamate exchange protein xCT within the nucleus accumbens core (NAcore). N-acetylcysteine (NAC) has been shown to restore these proteins in a rodent model of drug addiction and relapse. However, the specific molecular mechanisms driving its inhibitory effects on cue-induced nicotine reinstatement are unknown. Here, we confirm that extinction of nicotine-seeking behavior is associated with impaired NAcore GLT-1 function and expression and demonstrates that reinstatement of nicotine seeking rapidly enhances membrane fraction GLT-1 expression. Extinction and cue-induced reinstatement of nicotine seeking was also associated with increased tumor necrosis factor alpha (TNFα) and decreased glial fibrillary acidic protein (GFAP) expression in the NAcore. NAC treatment (100 mg/kg/day, i.p., for 5 d) inhibited cue-induced nicotine seeking and suppressed AMPA to NMDA current ratios, suggesting that NAC reduces NAcore postsynaptic excitability. In separate experiments, rats received NAC and an antisense vivo-morpholino to selectively suppress GLT-1 expression in the NAcore during extinction and were subsequently tested for cue-induced reinstatement of nicotine seeking. NAC treatment rescued NAcore GLT-1 expression and attenuated cue-induced nicotine seeking, which was blocked by GLT-1 antisense. NAC also reduced TNFα expression in the NAcore. Viral manipulation of the NF-κB pathway, which is downstream of TNFα, revealed that cue-induced nicotine seeking is regulated by NF-κB pathway signaling in the NAcore independent of GLT-1 expression. Ultimately, these results are the first to show that immunomodulatory mechanisms may regulate known nicotine-induced alterations in glutamatergic plasticity that mediate cue-induced nicotine-seeking behavior.
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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.