Abstract

Ketamine has been shown to acutely and rapidly ameliorate depressive symptoms and suicidality. Given that women suffer from depression at two-times the rate of men, the current work first reviews the literature at the intersection between two subjects: the neurobiological mechanisms of ketamine’s antidepressant effects, and how ovarian hormones might
interact with these phenomena. The neuroinflammatory hypothesis of depression is emphasized. Next, we investigated how the ovarian hormones 17β-estradiol and progesterone interact with ketamine’s effects on ovariectomized female Wistar rat behavior in the forced swim test. A secondary experiment analyzed the effects of ketamine on males, also in the forced swim test. No significant interaction or main
effects were found among the females, whereas ketamine significantly reduced immobility among the males. Locomotor activity recordings confirmed that ketamine’s effects in the forced swim test were not due to overall locomotor suppression.