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(2)), but progestins naturally co-vary 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 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 17beta-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 4h later, than did control rats administered vehicle (sesame oil 0.2 cc). Experiment 4: ovx rats administered E(2) or P with a 1.5h 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)alpha and beta isoforms, or propyl pyrazole triol (PPT; 0.9 mg/kg, sc), which is more selective for ERalpha than ERbeta, had significantly better performance in the object placement task than did rats administered vehicle or diarylpropionitrile (DPN; 0.9 mg/kg, sc), an ERbeta selective ligand. Experiment 6: ovx rats administered P, or its metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-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 ERalpha selective ER modulator PPT, P, or its metabolite, 3alpha,5alpha-THP, are administered post-training.
Frye
Cheryl A
CA
Department of Psychology, The University at Albany - State University of New York, United States. cafrye@albany.edu
Duffy
Caryn K
CK
Walf
Alicia A
AA
D000818:Animals; D004967:Estrogens / Q000494:pharmacology*; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D007858:Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D010052:Ovariectomy; D011280:Pregnanolone / Q000494:pharmacology*; D011372:Progestins / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013028:Space Perception / Q000187:drug effects*
D004967:Estrogens; D011372:Progestins; D020845:Selective Estrogen Receptor Modulators; D011280:Pregnanolone