ArticleBiological psychiatry2016
Sex Differences in Effects of Ketamine on Behavior, Spine Density, and Synaptic Proteins in Socially Isolated Rats.
Article in Biological psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 1 of them a synthesis that pooled it.
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Who cites it
94 citing papers in PubMed, 1 synthesis or guideline pooled it, 140 citations in OpenAlex.
- Alterations in brain synaptic proteins and mRNAs in mood disorders: a systematic review and meta-analysis of postmortem brain studies.Molecular psychiatry · 2022Pooled it
- Sex-dependent metabolism of ketamine and (Journal of psychopharmacology (Oxford, England) · 2022Trial
- Translating the immediate effects of S-Ketamine using hippocampal subfield analysis in healthy subjects-results of a randomized controlled trial.Translational psychiatry · 2021Trial
- Sex differences in response to ketamine as a rapidly acting intervention for treatment resistant depression.Journal of psychiatric research · 2019Trial
- Synaptic Plasticity-Intrinsic Excitability and Antidepressant Discovery.Biomedicines · 2026Review
- Ketamine Improves Anhedonic Phenotypes Across Species: Translational Evidence From the Probabilistic Reward Task.Biological psychiatry global open science · 2026Article
- Sex and individual differences in ketamine's effects on alcohol drinking in rats.Alcohol, clinical & experimental research · 2026Article
- Negative allosteric modulation of α5-GABAbioRxiv : the preprint server for biology · 2026Article
- 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
- The effects of ketamine on methamphetamine withdrawal-induced anxiety and drug-seeking behaviors in the rat.Drug and alcohol dependence · 2025Article
- Ketamine and Hydroxynorketamine: The Complex Balancing Act Within Fear Neural Ensembles.Biological psychiatry · 2025Article
- Effects of Subanesthetic Intravenous Ketamine Infusion on Stress Hormones and Synaptic Density in Rats with Mild Closed-Head Injury.Biomedicines · 2025Article
- Article
- Fast-acting antidepressant-like effects of ketamine in aged male rats.Pharmacological reports : PR · 2024Article
- Effects of Mild Closed-Head Injury and Subanesthetic Ketamine Infusion on Microglia, Axonal Injury, and Synaptic Density in Sprague-Dawley Rats.International journal of molecular sciences · 2024Article
- Ketamine ameliorates activity-based anorexia of adolescent female mice through changes in GluN2B-containing NMDA receptors at postsynaptic cytoplasmic locations of pyramidal neurons and interneurons of medial prefrontal cortex.Brain structure & function · 2024Article
- Sex dependence of opioid-mediated responses to subanesthetic ketamine in rats.Nature communications · 2024Article
- Ketamine Produces Antidepressant Effects by Inhibiting Histone Deacetylases and Upregulating Hippocampal Brain-Derived Neurotrophic Factor Levels in a Diisopropyl Fluorophosphate-Based Rat Model of Gulf War Illness.The Journal of pharmacology and experimental therapeutics · 2024Article
- Sex Differences in Stress Response: Classical Mechanisms and Beyond.Current neuropharmacology · 2024Article
- Aromatase inhibition and ketamine in rats: sex-differences in antidepressant-like efficacy.Biology of sex differences · 2023Article
34 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe mechanistic underpinnings of sex differences in occurrence of depression and efficacy of antidepressant treatments are poorly understood. We examined the effects of isolation stress (IS) and the fast-acting antidepressant ketamine on anhedonia and depression-like behavior, spine density, and synaptic proteins in male and female rats.
methodsWe used a chronic social IS paradigm to test the effects of ketamine (0, 2.5 mg/kg, and 5 mg/kg) on behavior and levels of synaptic proteins synapsin-1, postsynaptic density protein 95, and glutamate receptor 1 in male rats and female rats in diestrus. Medial prefrontal cortex spine density was also examined in male rats and female rats that received ketamine during either the diestrus or the proestrus phase of their estrous cycle.
resultsMale rats showed anhedonia and depression-like behavior after 8 weeks of IS, concomitant with decreases in spine density and levels of synapsin-1, postsynaptic density protein 95, and glutamate receptor 1 in the medial prefrontal cortex; these changes were reversed by a single injection of ketamine (5 mg/kg). After 11 weeks of IS, female rats showed depression-like behavior but no signs of anhedonia. Although both doses of ketamine rescued depression-like behavior in female rats, the decline observed in synaptic proteins and spine density in IS and in diestrus female rats could not be reversed by ketamine. Spine density was higher in female rats during proestrus than in diestrus.
conclusionsOur findings implicate a role for synaptic proteins synapsin-1, postsynaptic density protein 95, and glutamate receptor 1 and medial prefrontal cortex spine density in the antidepressant effects of ketamine in male rats subjected to IS but not in female rats subjected to IS, suggesting dissimilar underlying mechanisms for efficacy of ketamine in the two sexes.
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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.