ArticleAmino acids2016
Clavulanic acid enhances glutamate transporter subtype I (GLT-1) expression and decreases reinforcing efficacy of cocaine in mice.
Article in Amino acids, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1B Double Blind, Placebo (PBO) Controlled, Pharmaco- Magnetic Resonance Spectroscopy (MRS) Inpatient Study of Clavulanic Acid (CLAV) 500, 750, 1000 mg Daily Repeated Administration in Early Remitted Cocaine Use Disorder Subjects
A Randomized, Double-Blind, Placebo-Controlled Phase 2a Pilot Study to Assess the Efficacy and Safety of Clavulanic Acid vs. Placebo for the Treatment of Cocaine Use Disorder
Who cites it
30 citing papers in PubMed, 50 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
- Efficacy signals in a 12-week trial of clavulanic acid to decrease cocaine use.Drug and alcohol dependence · 2026Trial
- Impact of antibiotic-induced gut microbiota modulation on morphine analgesia, tolerance, withdrawal, and neurophysiological changes in mice.Scientific reports · 2025Article
- Clavulanic acid prevents paclitaxel-induced neuropathic pain through a systemic and central anti-inflammatory effect in mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Positive allosteric modulation of glutamate transporter reduces cocaine-induced locomotion and expression of cocaine conditioned place preference in rats.European journal of pharmacology · 2024Article
- Clavulanic acid inhibits methamphetamine locomotor sensitization in mice and normalizes methamphetamine-induced changes in glutaminase mRNA levels in the nucleus accumbens.Physiology & behavior · 2024Article
- Neuroimmune modulators as novel pharmacotherapies for substance use disorders.Brain, behavior, & immunity - health · 2024Article
- Clavulanic Acid-Mediated Increases in Anterior Cingulate Glutamate Levels are Associated With Decreased Cocaine Craving and Brain Network Functional Connectivity Changes.Current therapeutic research, clinical and experimental · 2024Article
- Clavulanic Acid: A Novel Potential Agent in Prevention and Treatment of Scopolamine-Induced Alzheimer's Disease.ACS omega · 2022Article
- The GLT-1 enhancer clavulanic acid suppresses cocaine place preference behavior and reduces GCPII activity and protein levels in the rat nucleus accumbens.Drug and alcohol dependence · 2022Article
- Clavulanic Acid Attenuating Effect on the Diabetic Neuropathic Pain in Rats.Neurochemical research · 2021Article
- Evidence for Modulation of Substance Use Disorders by the Gut Microbiome: Hidden in Plain Sight.Pharmacological reviews · 2021Review
- Glutamate homeostasis and dopamine signaling: Implications for psychostimulant addiction behavior.Neurochemistry international · 2021Review
- Ampicillin/Sulbactam Treatment Modulates NMDA Receptor NR2B Subunit and Attenuates Neuroinflammation and Alcohol Intake in Male High Alcohol Drinking Rats.Biomolecules · 2020Article
- Clavulanic acid improves ethanol withdrawal symptoms in rats.Iranian journal of basic medical sciences · 2020Article
- Novel Positive Allosteric Modulators of Glutamate Transport Have Neuroprotective Properties in an in Vitro Excitotoxic Model.ACS chemical neuroscience · 2019Article
- Effects of chronic cocaine self-administration and N-acetylcysteine on learning, cognitive flexibility, and reinstatement in nonhuman primates.Psychopharmacology · 2019Article
- The effects of clavulanic acid and amoxicillin on cue-primed reinstatement of cocaine seeking.Behavioral neuroscience · 2019Article
- Neuroimmune signaling in alcohol use disorder.Pharmacology, biochemistry, and behavior · 2019Review
- β-lactams modulate astroglial glutamate transporters and attenuate dependence to CP 55,940, a CB1 receptor agonist, in rat model.Behavioural brain research · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The β-lactam antibiotic ceftriaxone (CTX) reduces cocaine reinforcement and relapse in preclinical assays through a mechanism involving activation of glutamate transporter subtype 1 (GLT-1). However, its poor brain penetrability and intravenous administration route may limit its therapeutic utility for indications related to CNS diseases. An alternative is clavulanic acid (CA), a structural analog of CTX that retains the β-lactam core required for GLT-1 activity but displays enhanced brain penetrability and oral activity relative to CTX. Here, we tested the hypothesis that CA (1, 10 mg/kg ip) would enhance GLT-1 expression and decrease cocaine self-administration (SA) in mice, but at lower doses than CTX. Experiments revealed that GLT-1 transporter expression in the nucleus accumbens of mice treated with repeated CA (1, 10 mg/kg) was enhanced relative to saline-treated mice. Repeated CA treatment (1 mg/kg) reduced the reinforcing efficacy of cocaine (0.56 mg/kg/inf) in mice maintained on a progressive-ratio (PR) schedule of reinforcement but did not affect acquisition of cocaine SA under fixed-ratio responding or acquisition or retention of learning. These findings suggest that the β-lactamase inhibitor CA can activate the cellular glutamate reuptake system in the brain reward circuit and reduce cocaine's reinforcing efficacy at 100-fold lower doses than CTX.
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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.