ArticleThe international journal of neuropsychopharmacology2023
Sex and Estrous Cycle Are Not Mediators of S-Ketamine's Rapid-Antidepressant Behavioral Effects in a Genetic Rat Model of Depression.
Article in The international journal of neuropsychopharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 11 citations in OpenAlex.
- (R)-Ketamine reduces alcohol intake and alcohol seeking induced by reconsolidation of alcohol-related memories in female Marchigian Sardinian alcohol-preferring rats.Psychopharmacology · 2026Article
- Sex-specific difference on anxiety- and depressive-like behavior in neuronal growth regulator 1-knockout mice.Biology of sex differences · 2026Article
- A single S-ketamine injection enhances mTOR signaling in rat skeletal muscle.Journal of muscle research and cell motility · 2026Article
- Ultrasonic vocalisations in the Flinders Sensitive Line rat, a genetic animal model of depression.Acta neuropsychiatrica · 2025Article
- Exploring the Molecular Targets for the Antidepressant and Antisuicidal Effects of Ketamine Enantiomers by Using Network Pharmacology and Molecular Docking.Pharmaceuticals (Basel, Switzerland) · 2023Article
- The antidepressant actions of ketamine and its enantiomers.Pharmacology & therapeutics · 2023Review
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6 authors at 1 institution in 1 country.
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Abstract
backgroundRecent preclinical and clinical studies have shed light on the possible impact of sex and estrous/menstrual cycle on ketamine's antidepressant action but with incongruous results. The preclinical studies that have shown the effects of ovarian sex hormones have not done so in animal models of depression. Thus, the aim of the present study is to scrutinize the acute behavioral responses to a subanesthetic dose of S-ketamine in males vs females and in different estrous phases in free-cycling females in a well-powered translational approach.
methodsWe evaluated the behavioral sensitivity to 20 mg/kg S-ketamine (i.p.) in male and female Flinders Sensitive Line rats (FSLs) and their counterpart Flinders Resistant Line rats (FRLs) subjected to the open field and forced swim tests. Female rats were disaggregated into different estrous phases, and the behavioral outcomes were compared.
resultsAcute administration of S-ketamine had robust antidepressant-like effects in FSLs. Within our study power, we could not detect sex- or estrous cycle-specific different antidepressant-like responses to S-ketamine in FSLs. Fluctuations in the levels of ovarian sex hormones across different estrous cycles did not behaviorally affect S-ketamine's rapid-acting antidepressant mode of action. No sex-related or estrous cycle-related impact on behavioral despair was observed even among FRLs and saline-treated FSLs.
conclusionsWe conclude that physiological oscillations of estrogen and progesterone levels neither amplify nor diminish the behavioral antidepressant-like effect of S-ketamine. In addition, fluctuations of ovarian sex hormones do not predispose female animals to exhibit enhanced or reduced depressive-like and anxiety-like behaviors.
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