ArticleNature communications2024
Sex dependence of opioid-mediated responses to subanesthetic ketamine in rats.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 1 synthesis or guideline 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
- Effect of naltrexone pretreatment on ketamine-induced glutamatergic activity and symptoms of depression: a randomized crossover study.Nature medicine · 2025Trial
- Sex differences in placebo and antidepressant response to intranasal esketamine for treatment-resistant depression.Molecular psychiatry · 2026Article
- Bayesian-enhanced closed-loop optimization of ultrasound protocols for targeted and precise neuromodulation.bioRxiv : the preprint server for biology · 2026Article
- Functional Ultrasound Localization Microscopy on Freely Moving Rats.Research square · 2026Article
- Mechanism-guided identification of antidepressant G protein-coupled receptor drug targets.Cell · 2026Article
- Imaging of Neurovascular Activity during Motor Responses Evoked by Displacement-guided Focused Ultrasound (DgFUS) Neuromodulation in Mice.Research square · 2026Article
- Opioid-specific brain connectivity dynamics distinguish analgesia from secondary effects: Studies in male mice.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Esketamine/Ketamine: Dual-Action Mechanisms and Clinical Prospects beyond Anesthesia in Psychiatry, Immunology, and Oncology.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Acoustically activatable liposomes as a translational nanotechnology for site-targeted drug delivery and noninvasive neuromodulation.Nature nanotechnology · 2025Article
- 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
- Exploring Neural Dynamics in the Auditory Telencephalon of Crows Using Functional Ultrasound Imaging.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Transcranial brain-wide functional ultrasound and ultrasound localization microscopy in mice using multi-array probes.Scientific reports · 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
- Differential effects of statins on the anti-dyskinetic activity of sub-anesthetic ketamine.Neuroscience letters · 2025Article
- Beyond NMDA Receptors: A Narrative Review of Ketamine's Rapid and Multifaceted Mechanisms in Depression Treatment.International journal of molecular sciences · 2024Review
- Differential effects of opioid receptor antagonism on the anti-dyskinetic and anti-parkinsonian effects of sub-anesthetic ketamine treatment in a preclinical model.Neuropharmacology · 2024Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Subanesthetic ketamine is increasingly used for the treatment of varied psychiatric conditions, both on- and off-label. While it is commonly classified as an N-methyl D-aspartate receptor (NMDAR) antagonist, our picture of ketamine's mechanistic underpinnings is incomplete. Recent clinical evidence has indicated, controversially, that a component of the efficacy of subanesthetic ketamine may be opioid dependent. Using pharmacological functional ultrasound imaging in rats, we found that blocking opioid receptors suppressed neurophysiologic changes evoked by ketamine, but not by a more selective NMDAR antagonist, in limbic regions implicated in the pathophysiology of depression and in reward processing. Importantly, this opioid-dependent response was strongly sex-dependent, as it was not evident in female subjects and was fully reversed by surgical removal of the male gonads. We observed similar sex-dependent effects of opioid blockade affecting ketamine-evoked postsynaptic density and behavioral sensitization, as well as in opioid blockade-induced changes in opioid receptor density. Together, these results underscore the potential for ketamine to induce its affective responses via opioid signaling, and indicate that this opioid dependence may be strongly influenced by subject sex. These factors should be more directly assessed in future clinical trials.
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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.