ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2017
Contrasting the Role of xCT and GLT-1 Upregulation in the Ability of Ceftriaxone to Attenuate the Cue-Induced Reinstatement of Cocaine Seeking and Normalize AMPA Receptor Subunit Expression.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 78 citations in OpenAlex.
- A single extinction-based treatment with N-Acetylcysteine produces long-term reduction in cocaine relapse.Translational psychiatry · 2026Article
- Abstinence from cocaine self-administration promotes microglial pruning of astrocytes, which drives cocaine-seeking behavior.Cell reports · 2025Article
- Astrocytic HIV-1 Nef Expression Decreases Glutamate Transporter Expression in the Nucleus Accumbens and Increases Cocaine-Seeking Behavior in Rats.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Targeting Neuroplasticity in Substance Use Disorders: Implications for Therapeutics.Annual review of pharmacology and toxicology · 2025Review
- Astrocytic G Protein-Coupled Receptors in Drug Addiction.Engineering (Beijing, China) · 2025Article
- Ceftriaxone alters the gut microbiome composition and reduces alcohol intake in male and female Sprague-Dawley rats.Alcohol (Fayetteville, N.Y.) · 2024Article
- Glutamate dynamics in the dorsolateral striatum of rats with goal-directed and habitual cocaine-seeking behavior.Frontiers in molecular neuroscience · 2023Article
- Regulation of glutamate homeostasis in the nucleus accumbens by astrocytic CB1 receptors and its role in cocaine-motivated behaviors.Addiction neuroscience · 2022Article
- Role of suppressing GLT-1 and xCT in ceftriaxone-induced attenuation of relapse-like alcohol drinking in alcohol-preferring rats.Addiction biology · 2022Article
- Sulfasalazine decreases astrogliosis-mediated seizure burden.Epilepsia · 2022Article
- Elevation of Extracellular Glutamate by Blockade of Astrocyte Glutamate Transporters Inhibits Cocaine Reinforcement in Rats via a NMDA-GluN2B Receptor Mechanism.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Ceftriaxone as a Novel Therapeutic Agent for Hyperglutamatergic States: Bridging the Gap Between Preclinical Results and Clinical Translation.Frontiers in neuroscience · 2022Review
- Corticostriatal dysfunction and social interaction deficits in mice lacking the cystine/glutamate antiporter.Molecular psychiatry · 2021Article
- MC-100093, a NovelThe Journal of pharmacology and experimental therapeutics · 2021Article
- Extinction vs. Abstinence: A Review of the Molecular and Circuit Consequences of Different Post-Cocaine Experiences.International journal of molecular sciences · 2021Review
- Evidence for Modulation of Substance Use Disorders by the Gut Microbiome: Hidden in Plain Sight.Pharmacological reviews · 2021Review
- Role of prefrontal cortex projections to the nucleus accumbens core in mediating the effects of ceftriaxone on cue-induced cocaine seeking.Addiction biology · 2021Article
- Glutamate homeostasis and dopamine signaling: Implications for psychostimulant addiction behavior.Neurochemistry international · 2021Review
- Astrocytes as cellular mediators of cue reactivity in addiction.Current opinion in pharmacology · 2021Review
- Astrocyte Bioenergetics and Major Psychiatric Disorders.Advances in neurobiology · 2021Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Long-term treatment with ceftriaxone attenuates the reinstatement of cocaine seeking while increasing the function of the glutamate transporter 1 (GLT-1) and system xC- (Sxc) in the nucleus accumbens core (NAc). Sxc contributes the majority of nonsynaptic extracellular glutamate in the NAc, while GLT-1 is responsible for the majority of glutamate uptake. Here we used antisense to decrease the expression of GLT-1 and xCT (a catalytic subunit of Sxc) to determine the relative importance of both proteins in mediating the ability of ceftriaxone to prevent cue-induced reinstatement of cocaine seeking and normalize glutamatergic proteins in the NAc of rats. Intra-NAc xCT knockdown prevented ceftriaxone from attenuating reinstatement and from upregulating GLT-1 and resulted in increased surface expression of AMPA receptor subunits GluA1 and GluA2. Intra-NAc GLT-1 knockdown also prevented ceftriaxone from attenuating reinstatement and from upregulating xCT expression, without affecting GluA1 and GluA2 expression. In the absence of cocaine or ceftriaxone treatment, xCT knockdown in the NAc increased the expression of both GluA1 and GluA2 without affecting GLT-1 expression while GLT-1 knockdown had no effect. PCR and immunoprecipitation of GLT-1 revealed that ceftriaxone does not upregulate GLT-1 and xCT through a transcriptional mechanism, and their coregulation by ceftriaxone is not mediated by physical interaction. These data support important and distinct roles for xCT and GLT-1 in the actions of ceftriaxone and add to a body of literature finding evidence for coregulation of these transporters. Our results also point to xCT expression and subsequent basal glutamate levels as being a key mediator of AMPA receptor expression in the NAc.
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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.