Progesterone enhances learning and memory of aged wildtype and progestin receptor knockout mice

Progesterone can enhance cognitive performance among young and aged mice; however, the mechanisms underlying these effects of progesterone are not well-understood. Aged, mice which lack functional progestin receptors (PRKO), or wildtype mice were administered progesterone (10 mg/kg, SC), or vehicle, and learning/memory was evaluated. Progesterone, compared to vehicle, produced a conditioned place preference in PRKO and wildtype mice. Progesterone improved performance of PRKO and wildtype mice in the object placement, water maze, contextual and cued fear conditioning tasks. PRKO, compared to wildtype, mice performed better in the inhibitory avoidance task, irrespective of progesterone. Thus, progesterone to aged mice enhances performance across a variety of tasks and this may not require actions at PRs.