Progesterone to ovariectomized mice enhances cognitive performance in the spontaneous alternation, object recognition, but not placement, water maze, and contextual and cued conditioned fear tasks

Research on how steroid hormones mediate mnemonic processes have focused on effects of 17β-estradiol (E2); yet, progesterone (P4) co-varies with E2 across endogenous hormonal milieu, and itself may influence cognitive processes. We investigated the hypothesis that acute P4 treatment enhances cognitive performance compared to vehicle. Ovariectomized (OVX) c57/BL6J mice were randomly assigned to be subcutaneously injected with oil vehicle or P4 (10 mg/kg). Mice were trained in the spontaneous alternation, object recognition, object placement, water maze, or fear conditioning tasks, and injected with vehicle or P4 before training or immediately post-training, and then were tested 1, 4, or 24 h later. The data obtained from these experiments supported our hypothesis. P4 increased the percentage of spontaneous alterations made in a T-maze more so than did vehicle. P4, compared to vehicle, increased the percentage of time spent exploring the novel object in the object recognition task, but did not alter performance in the object placement task. P4, compared to vehicle, decreased latencies to reach the location in the water maze where the platform had been during training in a probe trial, but did not alter performance in the control, cued trial. Compared to vehicle, P4 treatment increased freezing in contextual and cued fear testing. Thus, acute P4 treatment to OVX mice can improve cognitive performance across a variety of tasks.