ArticleTranslational psychiatry2024
The endogenous opioid system in the medial prefrontal cortex mediates ketamine's antidepressant-like actions.
Article in Translational psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.
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Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 29 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
- Efficacy and safety of esketamine for pain control after cesarean delivery: a systematic review and meta-analysis of randomized controlled trials.Frontiers in pharmacology · 2025Pooled it
- Effect of naltrexone pretreatment on ketamine-induced glutamatergic activity and symptoms of depression: a randomized crossover study.Nature medicine · 2025Trial
- Structural basis of opioid receptor activation by PCP and ketamine.Nature structural & molecular biology · 2026Article
- Pleiotropic modulation of the gut-brain-lung axis by ketamine and its enantiomers.Molecular psychiatry · 2026Review
- Bifunctional Modulation of NMDA and Opioid Receptors in Ketamine Reinforcement and Misuse: Implications for Substance Use Disorder Treatment.Biological psychiatry · 2026Review
- Anesthetics as emerging therapeutics for post-traumatic stress disorder (PTSD): bridging bench and bedside.Molecular psychiatry · 2026Review
- Low Dose Ketamine Preconditions Astrocyte Mitochondria to Achieve Antidepressant Efficacy via Adenosine, Humanin, and Melatonin Upregulation and Efflux.Alpha psychiatry · 2026Article
- Time-dependent effects of rapid-acting antidepressants in iPSC-derived neurons from treatment-resistant depression and healthy volunteers.Molecular psychiatry · 2026Article
- Stress-induced motivational impairment is marked by diminished frontocortical cellular communication and neuropeptide signaling.bioRxiv : the preprint server for biology · 2026Article
- Mechanism-guided identification of antidepressant G protein-coupled receptor drug targets.Cell · 2026Article
- Kappa-Opioid Receptor Antagonism Prolongs the Antidepressant Effects of Ketamine in Adult Mice with Depression-like Behavior Induced by Adolescent Chronic Unpredictable Stress.International journal of molecular sciences · 2026Article
- Time-Dependent Effects of Rapid-Acting Antidepressants in iPSC-Derived Neurons from Treatment-Resistant Depression and Healthy Volunteers.Research square · 2026Article
- Buprenorphine initiation from fentanyl using low-dose intramuscular ketamine: a pilot study.Addiction science & clinical practice · 2026Article
- Antidepressants and the endogenous opioid system.Biochemical pharmacology · 2025Review
- The therapeutic potential of psilocybin beyond psychedelia through shared mechanisms with ketamine.Molecular psychiatry · 2025Review
- Ketamine Evokes Acute Behavioral Effects Via μ Opioid Receptor-Expressing Neurons of the Central Amygdala.Biological psychiatry · 2025Article
- Ketamine in clinical practice: transitioning from anesthetic agent to psychiatric therapeutic.CNS spectrums · 2025Review
- Redefining Ketamine Pharmacology for Antidepressant Action: Synergistic NMDA and Opioid Receptor Interactions?The American journal of psychiatry · 2025Review
- Ketamine and Major Ketamine Metabolites Function as Allosteric Modulators of Opioid Receptors.Molecular pharmacology · 2024Article
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4 authors at 1 institution in 1 country.
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Abstract
Recent studies have implicated the endogenous opioid system in the antidepressant actions of ketamine, but the underlying mechanisms remain unclear. We used a combination of pharmacological, behavioral, and molecular approaches in rats to test the contribution of the prefrontal endogenous opioid system to the antidepressant-like effects of a single dose of ketamine. Both the behavioral actions of ketamine and their molecular correlates in the medial prefrontal cortex (mPFC) are blocked by acute systemic administration of naltrexone, a competitive opioid receptor antagonist. Naltrexone delivered directly into the mPFC similarly disrupts the behavioral effects of ketamine. Ketamine treatment rapidly increases levels of β-endorphin and the expression of the μ-opioid receptor gene (Oprm1) in the mPFC, and the expression of gene that encodes proopiomelanocortin, the precursor of β-endorphin, in the hypothalamus, in vivo. Finally, neutralization of β-endorphin in the mPFC using a specific antibody prior to ketamine treatment abolishes both behavioral and molecular effects. Together, these findings indicate that presence of β-endorphin and activation of opioid receptors in the mPFC are required for the antidepressant-like actions of ketamine.
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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.