Progesterone reduces depressive behavior of young ovariectomized, aged progestin receptor knockout, and aged wild type mice in the tail suspension test.

Progestins may have effects to reduce depressive behavior, in part through actions of its metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP) at GABA(A) receptors, rather than through intracellular progestin receptors. In this study, we examined the effects of progesterone (10 mg/kg, subcutaneous injection) versus vehicle control (propylene glycol) on the depressive behavior of young and aged mice in the tail suspension test. In Experiment 1, we first characterized progesterone's anti-depressant effects by utilizing young (4-6-month-old) intact or ovariectomized female, and intact or gonadectomized male, C57BL/6 mice. Young female mice showed more depressive behavior than the young male mice. Compared with vehicle administration, progesterone reduced depressive behavior of ovariectomized female, but not male or intact female mice. In Experiment 2, mice were aged (20-24-month-old) intact wild type or progestin receptor knockout mice. Progestin receptor knockout mice showed less depressive behavior than wild type mice. Administration of progesterone to wild type and progestin receptor knockout mice reduced depressive behavior. Together, these data suggest that progesterone can decrease depressive behavior of young adult ovariectomized female, aged wild type and progestin receptor knockout mice. Thus, progesterone's effect to reduce depressive behavior of aged mice may not require actions at the intracellular progestin receptors.