Impact of estrogen receptor alpha and beta agonists on delayed alternation in middle-aged rats
Publication Type: |
Journal Article |
Year of Publication: |
2010 |
Authors: |
Steven L. Neese, Donna L. Korol, John A. Katzenellenbogen, Susan L. Schantz |
Publication/Journal: |
Hormones and Behavior |
Keywords: |
aging, cognition, dsa, estrogen receptor agonists, working memory |
ISBN: |
0018-506X |
Abstract:
Estrogens act in the adult brain to modulate cognition, enhancing performance on some learning tests and impairing performance on others. Our previous research has revealed an impairing effect of chronic 17[beta]-estradiol treatment in young and aged rats on a prefrontally-mediated working memory task, delayed spatial alternation (DSA). Little is known about the mechanisms of these impairing effects. The current study examined the effects of selective estrogen receptor (ER) [alpha] or ER[beta] activation on DSA performance in middle-aged female rats. Ovariectomized 12 month old Long-Evans (LE) rats were treated by subcutaneous injection with the ER[alpha] agonist propyl pyrazole triol (PPT) or the ER[beta] agonist diarylpropionitrile (DPN) at 0.02, 0.08, or 0.20 mg/kg/day, or with oil vehicle and tested on an operant variable delay DSA task. A 17[beta]-estradiol group (10% in cholesterol) was included as a positive control group. We replicated our previous finding of a 17[beta]-estradiol induced deficit on DSA performance and this effect was paralleled by low dose (0.02 mg/kg/day) DPN treatment. Higher doses of DPN failed to produce a significant change in performance. The highest dose of PPT (0.20 mg/kg/day) also impaired performance, but this effect was subtle and limited to the longest delay during the final block of testing. These data confirm our earlier findings that chronic 17[beta]-estradiol treatment has an impairing effect on the DSA task, and suggest that ER[beta] activation may underlie the deficit.