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 (E,), but progestins naturally co-vary with E, and may also influence cognitive performance. Spatial performance in the object placement task over endogenous hormonal states in which E, 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 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 17 beta-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 h later, than did control rats administered vehicle (sesame oil 0.2 cc). Experiment 4: ovx rats administered E-2 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 E,, which has a high affinity for both E-2 receptor (ER)alpha and beta isoforms, or propyl pyrazole triol (PPT; 0.9 mg/kg, sc), which is more selective for ER alpha than ER beta, had significantly better performance in the object placement task than did rats administered vehicle or diarylpropionitrile (DPN; 0.9 mg/kg, sc), an ER beta selective ligand. Experiment 6: ovx rats administered P, or its metabolite, 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha,5 alpha-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 ER alpha selective ER modulator PPT, P, or its metabolite, 3a,5a-THP, are administered post-training. (C) 2007 Elsevier Inc. All rights reserved.