Steroid modulation of cognitive function has focused on estrogen (E 2 ), but progestins naturally covary with E 2 and may also influence cognitive performance. Spatial performance in the object placement task over endogenous hormonal states in which E 2 and progestins vary, and when E 2 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 diestrous 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 E 2 and P, immediately after training in the object placement task, performed significantly better when tested 4 hours later, than did control rats administered vehicle (sesame oil 0.2 cc). Experiment 4: Ovx rats administered E 2 or P with a one and a half hour delay after training in the object placement task, did not perform differently than vehicle-administered controls. Experiment 5: Ovx rats administered post-training E 2 , which has a high affinity for both E 2 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 E 2 and/or P are naturally elevated or when E 2 , the ERα selective ER modulator PPT, P, or its metabolite, 3α,5α-THP, are administered post-training.
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