Figure 1.

Experimental timeline. Female Fischer 344 rats were received at 14 months of age and lavaged to examine the estrous cycle before removal of the ovaries at 15 months. Five to 6 weeks after OVX, the animals were behaviorally tested in the spatial water maze and assigned to ER or EB/oil treatment groups. Eight weeks later, 14 weeks after OVX, stereotaxic surgery was used to deliver viral vectors encoding ERα, ERβ, or GFP bilaterally into the dorsal hippocampi. The animals were allowed 1 week to recover and were then given cyclic injections of EB or oil for 5 weeks. Final behavioral assessment in the water maze was at 20 months of age and initiated 48 h after the seventh cycle of EB/oil treatment. Cyclic EB/oil treatments continued (1–7 additional cycles) and rats were sacrificed (Sac) 48 h after a final EB/oil treatment for electrophysiology, histology, and Western blot analysis.