S-ketamine exerts sex- and dose-dependent anti-compulsive-like effect as monotherapy or in augmentation to fluoxetine.
Júlia Grigorini Mori Ayub, C. Tosta, Breno Lopes Macedo, Tattyanna Fernandes Barreto, Lorena Martins Lopes, M. Fracalossi, R. Andreatini, V. Beijamini
European Journal of Pharmacology November 1, 2022 DOI: 10.1016/j.ejphar.2022.175382 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Adult female and male Swiss mice |
| Interventions | S-ketamine fluoxetine |
| Dose | 30 mg/kg |
| Topics | Esketamine Ketamine |
| Key points | Female mice are less sensitive to S-ketamine's anti-compulsive-like effect than male mice, and this difference is not explained by oscillations in female sex hormones. |
Abstract
Since a significant body of studies supports the involvement of glutamatergic neurotransmission in the neurobiology of obsessive-compulsive disorder (OCD). Ketamine, a glutamate N-methyl-D-aspartate (NMDA) receptor antagonist with rapid and sustained antidepressant effect, raises as a potential new anti-OCD drug. Evidence from pre-clinical studies indicates that female mice are more sensitive than male mice to ketamine antidepressant effects. Our group previously showed that S-ketamine, one ketamine enantiomer, induces an acute anti-compulsive effect in male mice. Herein, we investigated this S-ketamine effect in female adult Swiss mice as monotherapy or as an adjuvant to fluoxetine, a selective serotonin reuptake inhibitor (SSRI), compared to male mice. For this purpose, we assessed the S-ketamine anti-compulsive-like effect in the marble-burying (MBT) and nest-building (NBT) tests in adult female Swiss mice. S-ketamine reduced the compulsive-like behaviour of female mice in both animal tests in a dose larger (30 mg/kg) than the effective dose in male Swiss mice (10 mg/kg, Tosta et al., 2019). The association of sub-effective doses of S-ketamine and fluoxetine effectively reduced the marble-burying behaviour of both male and female Swiss mice, although male mice present a better response. The variation of female sex hormones (oestrogen and progesterone), inferred by oestrous cycle and ovariectomy, did not influence S-ketamine's response. In conclusion, we found that female mice are less sensitive to S-ketamine's anti-compulsive-like effect than male mice as monotherapy or adjuvant treatment, but oscillations in female sex hormones concentrations do not seem to explain this difference.
Comparable studies
Other preclinical and animal studies on esketamine, most cited first.
Citations in the library
Cited by 2
- Increased Kcnq2 in the hippocampal contributes to esketamine-induced long-term cognitive dysfunction in neonatal mice. Journal of Affective Disorders June 8, 2025
- Ketamine and Esketamine in Obsessive-Compulsive Disorder: A Scoping Review of Clinical and Mechanistic Evidence. Pharmaceuticals April 16, 2026
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