Estrogen receptor alpha (ERα) partially modulates ketamine's sustained anxiolytic effects without altering its antidepressant properties in female rats.
Psychoneuroendocrinology July 1, 2025 Ece Idil, Bahar Yuksel, Zeynep Sen et al. 2 citations
Ketamine works faster as an antidepressant in females than in males, and this sex difference has been linked to ovarian hormones and faster metabolism in females. In adult female Wistar rats, blocking estrogen receptor alpha (ERα) with the antagonist MPP before a single antidepressant dose of ketamine did not prevent ketamine from reducing behavioral despair in the forced swim test. ERα antagonism and ketamine together showed a possible interaction on anxiety-like behaviors in the open field and elevated plus maze, but this effect was not statistically significant. Neither treatment affected fear memory. The results indicate that the sex-specific antidepressant effects of ketamine do not depend on ERα activity, though ERα may still influence anxiety-related brain circuits.