Distinct effects of estrogen receptor antagonism on object recognition and spatial memory consolidation in...

Exogenous treatment with the potent estrogen 17β-estradiol (E₂) or selective estrogen receptor α/β (ERα/β) agonists enhances the consolidation of hippocampal-dependent object recognition (OR) and object placement (OP) memories in ovariectomized rodents. Although such data suggest that individual ERs are sufficient for memory consolidation, the necessity of a given ER for memory consolidation can only be demonstrated by blocking receptor function, for example with an ER antagonist. However, the effects on memory of antagonizing ERα or ERβ function are not well understood. Moreover, ER antagonism in ovariectomized subjects also provides indirect information about the role of individual ERs in the memory-enhancing effects of local hippocampal E₂ synthesis. Therefore, this study used pharmacological inhibition of ERα and ERβ to elucidate the importance of each ER to memory consolidation. Specifically, we examined effects on OR and OP memory consolidation of immediate post-training dorsal hippocampal (DH) infusion of MPP and PHTPP, selective antagonists for ERα and ERβ, respectively. Each drug exhibited a distinct effect on OR and OP. DH infusion of MPP (0.28 or 2.78ng/hemisphere) impaired memory in OP, but not OR. However, DH infusion of PHTPP (0.21 or 2.12ng/hemisphere) impaired memory in both OR and OP. Neither drug affected the elapsed time to accumulate object exploration in either task, suggesting a specific effect on memory. These results indicate that activation of either classical ER within the dorsal hippocampus is important for hippocampal memory consolidation in ovariectomized mice, but suggest that specific ER involvement is memory- or task-specific. The findings also indirectly support a role for ERα and ERβ in mediating the memory-enhancing effects of hippocampally-synthesized E₂.