Estrogens and progestins enhance spatial learning of intact and ovariectomized rats in the object placement task

Steroid modulation of cognitive function has focused on estrogen (E2), but progestins naturally co-vary with E2 and may also influence cognitive performance. Spatial performance in the object placement task over endogenous hormonal states in which E2 and progestins vary, and when E2 and/or progestins were administered, was examined. Experiment 1: Rats in proestrus or estrus had significantly better performance in the object placement task than did diestrus rats. Experiment 2: Rats in the third trimester, post-partum, or lactation exhibited significantly better performance in the object placement task than did rats in the first trimester. Experiment 3: Ovariectomized (ovx) rats administered 17β-estradiol (0.9 mg/kg), subcutaneously (sc), progesterone (P; 4 mg/kg, sc), or E2 and P, immediately after training in the object placement task, performed significantly better when tested 4 h later, than did control rats administered vehicle (sesame oil 0.2 cc). Experiment 4: ovx rats administered E2 or P with a 1.5 h delay after training in the object placement task, did not perform differently than vehicle-administered controls. Experiment 5: ovx rats administered post-training E2, which has a high affinity for both E2 receptor (ER)α and β isoforms, or propyl pyrazole triol (PPT; 0.9 mg/kg, sc), which is more selective for ERα than ERβ, had significantly better performance in the object placement task than did rats administered vehicle or diarylpropionitrile (DPN; 0.9 mg/kg, sc), an ERβ selective ligand. Experiment 6: ovx rats administered P, or its metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP; 4 mg/kg, sc), immediately post-training performed significantly better in the object placement task than did vehicle control rats. Thus, performance in the object placement task is better when E2 and/or P are naturally elevated or when E2, the ERα selective ER modulator PPT, P, or its metabolite, 3α,5α-THP, are administered post-training.