ArticleBiology of sex differences2023
Aromatase inhibition and ketamine in rats: sex-differences in antidepressant-like efficacy.
Article in Biology of sex differences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 12 citations in OpenAlex.
- Selective estrogen receptor modifiers on the antidepressant-like effects of electroconvulsive seizures in adolescent rats.Translational psychiatry · 2026Article
- The immunological perspective of major depressive disorder: unveiling the interactions between central and peripheral immune mechanisms.Journal of neuroinflammation · 2025Review
- Neuroplasticity and Mechanisms of Action of Acute and Chronic Treatment with Antidepressants in Preclinical Studies.Biomedicines · 2024Review
- Fast-acting antidepressant-like effects of ketamine in aged male rats.Pharmacological reports : PR · 2024Article
- Cannabidiol or ketamine for preventing the impact of adolescent early drug initiation on voluntary ethanol consumption in adulthood.Frontiers in pharmacology · 2024Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundKetamine has been recently approved to treat resistant depression; however preclinical studies showed sex differences in its efficacy. Sex steroids, such as estrogens and testosterone, both in the periphery and locally in the brain, are regarded as important modulators of these sex differences. Therefore, the present study evaluated how inhibiting the biosynthesis of estrogens with letrozole (an aromatase inhibitor) could affect the observed sex differences in ketamine's antidepressant-like-response.
methodsWe performed several consecutive studies in adult Sprague-Dawley rats to evaluate potential sex differences in the antidepressant-like effects of ketamine (5 mg/kg, 7 days, i.p.), letrozole (1 mg/kg, 8 days, i.p.) and their combination (letrozole pre-treatment 3 h before ketamine). Acute and repeated antidepressant-like responses were ascertained in a series of behavioral tests (forced-swim, novelty-suppressed feeding, two-bottle choice for sucrose preference).
resultsThe main results proved clear sex differences in the antidepressant-like response induced by ketamine, which was observed following a repeated paradigm in adult male rats, but rendered inefficacious in female rats. Moreover, decreasing estrogens production with letrozole induced on itself an antidepressant-like response in female rats, while also increased ketamine's response in male rats (i.e., quicker response observed after only a single dose). Interestingly, both the antidepressant-like effects induced by ketamine in male rats or letrozole in female rats persisted over time up to 65 days post-treatment, suggesting long-term sex-directed benefits for these drugs.
conclusionsThe present results demonstrated a sex-specific role for aromatase inhibition with letrozole in the antidepressant-like response induced by ketamine in male rats. Moreover, letrozole itself presented as a potential antidepressant for females with persistent effects over time. Clearly, the production of estrogens is key in modulating, in a sex-specific manner, affective-like responses and thus deserve further studies.
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