ArticleDrug and alcohol dependence2014
Clavulanic acid reduces rewarding, hyperthermic and locomotor-sensitizing effects of morphine in rats: a new indication for an old drug?
Article in Drug and alcohol dependence, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Troriluzole attenuates opioid intake, reinforcing efficacy, seeking behaviours, physical dependence and antinociceptive tolerance in rats.British journal of pharmacology · 2026Article
- Positive allosteric modulator of GLT-1 reduces methamphetamine hyperlocomotion, sensitization and conditioned place preference in mice.Neuroscience research · 2025Article
- Molecular and Behavioral Neuroprotective Effects of Clavulanic Acid and Crocin in Haloperidol-Induced Tardive Dyskinesia in Rats.Molecular neurobiology · 2025Article
- Clavulanic acid inhibits methamphetamine locomotor sensitization in mice and normalizes methamphetamine-induced changes in glutaminase mRNA levels in the nucleus accumbens.Physiology & behavior · 2024Article
- 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
- Glutamatergic Systems and Memory Mechanisms Underlying Opioid Addiction.Cold Spring Harbor perspectives in medicine · 2021Review
- Clavulanic acid improves ethanol withdrawal symptoms in rats.Iranian journal of basic medical sciences · 2020Article
- The Opioid-Addicted Tetrapartite Synapse.Biological psychiatry · 2020Review
- Neuroimmune signaling in alcohol use disorder.Pharmacology, biochemistry, and behavior · 2019Review
- Effects of Clavulanic Acid Treatment on Reinstatement to Methamphetamine, Glial Glutamate Transporters, and mGluR 2/3 Expression in P Rats Exposed to Ethanol.Journal of molecular neuroscience : MN · 2019Article
- Glutamate Transport: A New Bench to Bedside Mechanism for Treating Drug Abuse.The international journal of neuropsychopharmacology · 2017Review
- The Nucleus Accumbens: Mechanisms of Addiction across Drug Classes Reflect the Importance of Glutamate Homeostasis.Pharmacological reviews · 2016Review
- Clavulanic acid enhances glutamate transporter subtype I (GLT-1) expression and decreases reinforcing efficacy of cocaine in mice.Amino acids · 2016Article
- Amoxicillin and amoxicillin/clavulanate reduce ethanol intake and increase GLT-1 expression as well as AKT phosphorylation in mesocorticolimbic regions.Brain research · 2015Article
- Effect of ceftriaxone and topiramate treatments on naltrexone-precipitated morphine withdrawal and glutamate receptor desensitization in the rat locus coeruleus.Psychopharmacology · 2015Article
- Levamisole enhances the rewarding and locomotor-activating effects of cocaine in rats.Drug and alcohol dependence · 2015Article
- Glutamate Transporter GLT-1 as a Therapeutic Target for Substance Use Disorders.CNS & neurological disorders drug targets · 2015Review
- Upregulation of Glutamate Transporter 1 by Clavulanic Acid Administration and Attenuation of Allodynia and Hyperalgesia in Neuropathic Rats.Basic and clinical neuroscienceArticle
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundDespite the efficacy of ceftriaxone (CTX) in animal models of CNS diseases, including drug addiction, its utility as a CNS-active therapeutic may be limited by poor brain penetrability and cumbersome parenteral administration. An alternative is the β-lactamase inhibitor clavulanic acid (CA), a constituent of Augmentin that prevents antibiotic degradation. CA possesses the β-lactam core necessary for CNS activity but, relative to CTX, possesses: (1) oral activity; (2) 2.5-fold greater brain penetrability; and (3) negligible antibiotic activity.
methodsTo compare the effectiveness of CA (10mg/kg) and CTX (200mg/kg) against centrally-mediated endpoints, we investigated their effects against morphine's rewarding, hyperthermic, and locomotor-sensitizing actions. Endpoints were based on prior evidence that CTX attenuates morphine-induced physical dependence, tolerance, and hyperthermia.
resultsAs expected, rats treated with morphine (4 mg/kg) displayed hyperthermia and conditioned place preference (CPP). Co-treatment with CTX or CA inhibited development of morphine-induced CPP by approximately 70%. Morphine's hyperthermic effect was also suppressed, with CTX and CA producing 57% and 47% inhibition, respectively. Locomotor sensitization induced by repeated morphine exposures was inhibited by CA but not CTX.
conclusionsThe present findings are the first to suggest that CA disrupts the in vivo actions of morphine and point toward further studying CA as a potential therapy for drug addiction. Further, its ability to disrupt morphine's rewarding effects at 20-fold lower doses than CTX identifies CA as an existing, orally-active alternative to direct CTX therapy for CNS diseases.
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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.