ArticleNeuropharmacology2018
Behavioral and biochemical sensitivity to low doses of ketamine: Influence of estrous cycle in C57BL/6 mice.
Article in Neuropharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
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Who cites it
44 citing papers in PubMed, 73 citations in OpenAlex.
- Depression treatment response to ketamine: sex-specific role of interleukin-8, but not other inflammatory markers.Translational psychiatry · 2021Trial
- (R)-Ketamine reduces alcohol intake and alcohol seeking induced by reconsolidation of alcohol-related memories in female Marchigian Sardinian alcohol-preferring rats.Psychopharmacology · 2026Article
- The psychedelic phenethylamine 25C-NBF, a selective 5-HT2A agonist, shows psychoplastogenic properties and rapid antidepressant effects in male rodents.Molecular psychiatry · 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
- Ketamine Reverses Chronic Stress-Induced Behavioral Changes via the Expression of CaFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Article
- Exploring ketamine's reinforcement, cue-induced reinstatement, and nucleus accumbens cFos activation in male and female long evans rats.Neuropharmacology · 2024Article
- Practical solutions for including sex as a biological variable (SABV) in preclinical neuropsychopharmacological research.Journal of neuroscience methods · 2024Review
- Aromatase inhibition and ketamine in rats: sex-differences in antidepressant-like efficacy.Biology of sex differences · 2023Article
- CB1 Receptor Silencing Attenuates Ketamine-Induced Hyperlocomotion Without Compromising Its Antidepressant-Like Effects.Cannabis and cannabinoid research · 2023Article
- Exploring the Molecular Targets for the Antidepressant and Antisuicidal Effects of Ketamine Enantiomers by Using Network Pharmacology and Molecular Docking.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Article
- Sex and Estrous Cycle Are Not Mediators of S-Ketamine's Rapid-Antidepressant Behavioral Effects in a Genetic Rat Model of Depression.The international journal of neuropsychopharmacology · 2023Article
- Minimal influence of estrous cycle on studies of female mouse behaviors.Frontiers in molecular neuroscience · 2023Article
- Dose-dependent effects of esketamine on brain activity in awake mice: A BOLD phMRI study.Pharmacology research & perspectives · 2022Article
- Comparison of inflammatory and behavioral responses to chronic stress in female and male mice.Brain, behavior, and immunity · 2022Article
- Repeated ketamine anesthesia during neurodevelopment upregulates hippocampal activity and enhances drug reward in male mice.Communications biology · 2022Article
- Enhanced Fear Memories and Altered Brain Glucose Metabolism (International journal of molecular sciences · 2022Article
- Sex- and estrous-cycle dependent dorsal hippocampal phosphoproteomic changes induced by low-dose ketamine.Scientific reports · 2022Article
- Sex Differences in the Behavioral, Molecular, and Structural Effects of Ketamine Treatment in Depression.The international journal of neuropsychopharmacology · 2022Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
rationaleLow-dose ketamine is a rapid-acting antidepressant, to which female rodents are more sensitive as compared to males. However, the mechanism mediating this sex difference in ketamine sensitivity remains elusive.
objectivesWe sought to determine whether male and female mice differ in their behavioral sensitivity to low doses of ketamine, and uncover how ovarian hormones influence females' ketamine sensitivity. We also aimed to uncover some of the molecular mechanism(s) in mood-related brain regions that mediate sex differences in ketamine antidepressant effects.
methodsMale and female mice (freely-cycling, diestrus 1 [D1], proestrus [Pro], or D1 treated with an estrogen receptor (ER) α, ERβ, or progesterone receptor (PR) agonist) received ketamine (0, 1.5, or 3 mg/kg, intraperitoneally) and were tested in the forced swim test (FST) 30 min later. Ketamine's influence over synaptic plasticity markers in the prefrontal cortex (PFC) and hippocampus (HPC) of males, D1, and Pro females was quantified by Western blot 1 h post-treatment.
resultsMales, freely cycling females, D1 and Pro females exhibited antidepressant-like responses to 3 mg/kg ketamine. Pro females were the only group where ketamine exhibited an antidepressant effect at 1.5 mg/kg. D1 females treated with an agonist for ERα or ERβ exhibited an antidepressant-like response to 1.5 mg/kg ketamine. Ketamine (3 mg/kg) increased synaptic plasticity-related proteins in the PFC and HPC of males, D1, and Pro females. Yet, Pro females exhibited an increase in p-Akt and p-CaMKIIα in response to 1.5 and 3 mg/kg ketamine.
conclusionOur results indicate that females' enhanced sensitivity to ketamine during Pro is likely mediated through estradiol acting on ERα and ERβ, leading to greater activation of synaptic plasticity-related kinases within the PFC and HPC.
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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.