ArticleBiological psychiatry2023
Mu Opioid Receptor Activation Mediates (S)-ketamine Reinforcement in Rats: Implications for Abuse Liability.
Article in Biological psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Is the antidepressant efficacy of ketamine and esketamine mediated via opioid mechanisms?European psychiatry : the journal of the Association of European Psychiatrists · 2026Pooled it
- Antidepressant efficacy of ketamine plus naltrexone for major depression comorbid with alcohol use disorder: a randomized controlled trial.The international journal of neuropsychopharmacology · 2025Trial
- Efficacy of esketamine for the treatment of postpartum depression and pain control following cesarean section: a randomized, double-blind, controlled clinical trial.BMC anesthesiology · 2024Trial
- Structural basis of opioid receptor activation by PCP and ketamine.Nature structural & molecular biology · 2026Article
- Molecular snapshots confirm ketamine's opioid nature.Nature structural & molecular biology · 2026Article
- A crucial cautionary note on frequently incorrect dose equivalence between ketamine and esketamine.Molecular psychiatry · 2026Article
- Bifunctional Modulation of NMDA and Opioid Receptors in Ketamine Reinforcement and Misuse: Implications for Substance Use Disorder Treatment.Biological psychiatry · 2026Review
- Mechanism-guided identification of antidepressant G protein-coupled receptor drug targets.Cell · 2026Article
- Esketamine/Ketamine: Dual-Action Mechanisms and Clinical Prospects beyond Anesthesia in Psychiatry, Immunology, and Oncology.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Review
- Antidepressants and the endogenous opioid system.Biochemical pharmacology · 2025Review
- Ketamine-induced static and dynamic functional connectivity changes are modulated by opioid receptors and biological sex in rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Ketamine Evokes Acute Behavioral Effects Via μ Opioid Receptor-Expressing Neurons of the Central Amygdala.Biological psychiatry · 2025Article
- Esketamine in depression: putative biomarkers from clinical research.European archives of psychiatry and clinical neuroscience · 2025Review
- The dopaminergic effects of esketamine are mediated by a dual mechanism involving glutamate and opioid receptors.Molecular psychiatry · 2025Article
- Ketamine and Hydroxynorketamine as Novel Pharmacotherapies for the Treatment of Opioid Use Disorders.Biological psychiatry · 2025Review
- Redefining Ketamine Pharmacology for Antidepressant Action: Synergistic NMDA and Opioid Receptor Interactions?The American journal of psychiatry · 2025Review
- Insights for the Next Generation of Ketamine for the Treatment of Depressive Disorder.Journal of medicinal chemistry · 2025Review
- N-methyl-D-aspartate Receptors and Depression: Linking Psychopharmacology, Pathology and Physiology in a Unifying Hypothesis for the Epigenetic Code of Neural Plasticity.Pharmaceuticals (Basel, Switzerland) · 2024Review
- What should constitute a control condition in psychedelic drug trials?Nature. Mental health · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
background(S)-ketamine is an NMDA receptor antagonist, but it also binds to and activates mu opioid receptors (MORs) and kappa opioid receptors in vitro. However, the extent to which these receptors contribute to (S)-ketamine's in vivo pharmacology is unknown.
methodsWe investigated the extent to which (S)-ketamine interacts with opioid receptors in rats by combining in vitro and in vivo pharmacological approaches, in vivo molecular and functional imaging, and behavioral procedures relevant to human abuse liability.
resultsWe found that the preferential opioid receptor antagonist naltrexone decreased (S)-ketamine self-administration and (S)-ketamine-induced activation of the nucleus accumbens, a key brain reward region. A single reinforcing dose of (S)-ketamine occupied brain MORs in vivo, and repeated doses decreased MOR density and activity and decreased heroin reinforcement without producing changes in NMDA receptor or kappa opioid receptor density.
conclusionsThese results suggest that (S)-ketamine's abuse liability in humans is mediated in part by brain MORs.
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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.