ArticlePsychopharmacology2016
Metabolic shift of the kynurenine pathway impairs alcohol and cocaine seeking and relapse.
Article in Psychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06636227 (Optimal Dosing, Tolerability, and Initial Efficacy of Diclofenac as a KMO Inhibitor in Individuals With Alcohol Use Disorder), which is not on this map. Cited by 19 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.
Optimal Dosing, Tolerability, and Initial Efficacy of Diclofenac as a KMO Inhibitor in Individuals With Alcohol Use Disorder
Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Individual and additive effects of childhood maltreatment and substance use disorder histories on baseline and stress-induced changes in peripheral stress biomarkers.Psychopharmacology · 2026Article
- KMO Inhibition Improves Seizures and Depressive-like Behaviors Without Aggravating Cognitive Impairment in Epileptic Mice.Current issues in molecular biology · 2025Article
- Impact of Substance Use Disorder on Tryptophan Metabolism Through the Kynurenine Pathway: A Narrative Review.Metabolites · 2024Review
- Tryptophan and Substance Abuse: Mechanisms and Impact.International journal of molecular sciences · 2023Review
- Influx of kynurenine into the brain is involved in the reduction of ethanol consumption induced by Ro 61-8048 after chronic intermittent ethanol in mice.British journal of pharmacology · 2022Article
- FACTORS CONTRIBUTING TO THE ESCALATION OF ALCOHOL CONSUMPTION.Neuroscience and biobehavioral reviews · 2022Review
- Proteomics and weighted gene correlated network analysis reveal glutamatergic synapse signaling in diazepam treatment of alcohol withdrawal.Frontiers in pharmacology · 2022Article
- Alterations of kynurenine pathway in alcohol use disorder and abstinence: a link with gut microbiota, peripheral inflammation and psychological symptoms.Translational psychiatry · 2021Article
- Evidence for Modulation of Substance Use Disorders by the Gut Microbiome: Hidden in Plain Sight.Pharmacological reviews · 2021Review
- The Tryptophan System in Cocaine-Induced Depression.Journal of clinical medicine · 2020Article
- Sobriety and Satiety: Is NAD+ the Answer?Antioxidants (Basel, Switzerland) · 2020Review
- Serotonin is the main tryptophan metabolite associated with psychiatric comorbidity in abstinent cocaine-addicted patients.Scientific reports · 2019Article
- Changes in brain kynurenine levelsFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- NAD+ cellular redox and SIRT1 regulate the diurnal rhythms of tyrosine hydroxylase and conditioned cocaine reward.Molecular psychiatry · 2019Article
- Preclinical Studies of Cannabinoid Reward, Treatments for Cannabis Use Disorder, and Addiction-Related Effects of Cannabinoid Exposure.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Review
- Rat animal models for screening medications to treat alcohol use disorders.Neuropharmacology · 2017Review
- Reply to: kynurenic acid and alcohol and cocaine dependence: novel effects and multiple mechanisms?Psychopharmacology · 2017Article
- Kynurenine Pathway of Tryptophan Metabolism: Regulatory and Functional Aspects.International journal of tryptophan research : IJTR · 2017Review
- Kynurenic acid and alcohol and cocaine dependence: novel effects and multiple mechanisms?Psychopharmacology · 2017Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleThe glutamatergic system plays a key role in the maintenance of drug use and development of drug-related conditioned behaviours. In particular, hyper-glutamatergic activity and N-methyl-D-aspartate receptor (NMDAR) activation may drive drug craving and relapse. Inhibition of kynurenine-3-monooxygenase (KMO) shifts the metabolic kynurenine pathway towards production of kynurenic acid, which leads to a reduction of glutamatergic/NMDAR activity via different mechanisms.
objectivesIn this study, we investigated whether drug-seeking and relapse behaviour could be modified by the metabolic shift of endogenous kynurenine pathway.
methodsAn inhibitor of kynurenine-3-monooxygenase (KMO) Ro61-8048 (4 and 40 mg/kg) and its prodrug JM6 (100 and 200 mg/kg) were tested in two behavioural rat models for drug seeking and relapse-the alcohol deprivation effect (ADE) model in long-term alcohol-drinking rats and the model of cue-induced reinstatement of alcohol- and cocaine-seeking behaviour.
resultsOur results show that relapse-like alcohol drinking during the ADE was abolished by repeated intraperitoneal administration of Ro61-8048 and significantly reduced by its oral prodrug JM6. Cue-induced reinstatement of both alcohol- and cocaine-seeking behaviour was also abolished by administration of Ro61-8048.
conclusionsPharmacological enhancement of endogenous kynurenic acid levels provides a novel treatment strategy to interfere with glutamatergic/NMDAR activity as well as with craving and relapse in alcohol-dependent patients and drug addicts.
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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.