Progesterone, compared to medroxyprogesterone acetate, to C57BL/6, but not 5α-reductase mutant, mice enhances object recognition and placement memory and is associated with higher BDNF levels in the hippocampus and cortex.

Progesterone (P4) may influence cognition in part through actions of its 5α-reduced metabolite, allopregnanolone. Ovariectomized mice that were C57BL/6 wildtype (WT), or deficient in the 5α-reductase Type 1 enzyme (5α-reductase knockout; 5αRKO), were administered vehicle, P4, allopregnanolone, or medroxyprogesterone acetate (MPA) after training in the object recognition or placement tasks. WT mice administered P4 or allopregnanolone performed significantly better in the object recognition and placement tasks than did WT mice administered vehicle or MPA. 5αRKO mice administered allopregnanolone, but not P4, MPA, or vehicle showed enhanced performance in the object recognition and placement tasks. Levels of brain-derived neurotrophic factor (BDNF) in the prefrontal cortex and hippocampus were lowest among mice administered MPA. Thus, some of P4s effects to enhance cognitive performance may be incumbent upon its 5α-reduction.