Estradiol-induced enhancement of object memory consolidation involves hippocampal extracellular signal-regulated kinase activation and membrane-bound estrogen receptors - PubMed (original) (raw)

a, Time spent with the novel object 48 h after intracerebroventricular (ICV), intrahippocampal (IH), or intraperitoneal drug administration (bars for the familiar object are omitted for simplicity). Mice treated with intracerebroventricular 5 μ

BSA-E2 plus intrahippocampal 5 μg of ICI 182,780, 0.2 mg/kg E2 (intraperitoneal), intracerebroventricular 5 μ

BSA-E2 plus intrahippocampal vehicle, and intracerebroventricular vehicle plus intrahippocampal 5 μ

BSA-E2 spent significantly more time with the novel object than chance (dashed line at 15 s) after 48 h, demonstrating memory for the familiar object. All other groups failed to exhibit a significant preference for the novel object relative to chance. In brief, these data show that 0.2 mg/kg E2 and BSA-E2 administered into either the dorsal third ventricle or dorsal hippocampus enhance object recognition, and that ICI 182,780 can block the effects of E2, but not of BSA-E2, on object recognition. The data also show that ICI 182,780 does not act as an agonist in this task, and that dorsal hippocampal inactivation with muscimol reduces the beneficial effects of BSA-E2 on object memory. Each bar represents the mean (±SEM) time spent with each object (*p < 0.05 relative to chance). b, Phospho-p42 ERK levels in dorsal CA1 were measured 5 min after infusion in all groups but those receiving 0.2 mg/kg E2, in which mice were killed 60 min after E2 injection (5 min after ICI 182,780 infusion in the E2 plus ICI 182,780 group). Phospho-p42 ERK levels in dorsal CA1 were significantly increased relative to intracerebroventricular vehicle plus intrahippocampal vehicle controls in groups receiving 0.2 mg/kg E2, intracerebroventricular BSA-E2 plus intrahippocampal vehicle, and intracerebroventricular vehicle plus intrahippocampal BSA-E2 (*p < 0.05 relative to vehicle controls). Thus, administration of E2 or BSA-E2 alone significantly increased phospho-p42 ERK levels in dorsal CA1. Phospho-p42 ERK levels in other groups did not differ significantly from controls. Of note, levels in the intracerebroventricular BSA-E2 plus intrahippocampal ICI 182,780 group were not significantly different from vehicle controls or from the group receiving intracerebroventricular BSA-E2 plus intrahippocampal vehicle (+p < 0.05 relative to both groups), suggesting a partial blockade of the effects of BSA-E2 by ICI 182,780. Each bar represents mean (±SEM) percentage change from intracerebroventricular vehicle plus intrahippocampal vehicle controls. Inset, Representative Western blots showing phosphorylated p42 ERK protein levels (note that the order of the bands matches the order of the bars in the figure; group names are abbreviated for simplicity).