The ERK phosphorylation inhibitor U0126 did not block the memory-enhancing effects of E2 in intact or GDX males. The ERK phosphorylation inhibitor U0126.

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DH E2 infusion significantly increased phosphorylation of the p42 isoform of ERK (A) and of Akt (B) in the DH of OVX females, but not sham GDX males. DH.

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The ERK phosphorylation inhibitor U0126 did not block the memory-enhancing effects of E2 in intact or GDX males. The ERK phosphorylation inhibitor U0126 did not block the memory-enhancing effects of E2 in intact or GDX males. A, B, Three doses of U0126 were tested to find one that did not impair memory consolidation on its own. In both OP (A) and OR (B), 1.0 μg/hemisphere U0126 impaired memory consolidation, whereas 0.5 μg/hemisphere U0126 did not. As such, 0.5 μg/hemisphere U0126 was next co-infused with E2 to determine whether the beneficial effects of E2 on memory in males depended on ERK phosphorylation. C, D, Sham and GDX male mice receiving intracerebroventricular infusion of E2 spent significantly more time than chance (*p < 0.05; dashed line) exploring the moved or novel object in OP (C) and OR (D), regardless of whether they received a DH infusion of vehicle (Veh) or U0126. In contrast, mice receiving intracerebroventricular vehicle and DH vehicle or U0126 did not differ from chance in time spent with the moved and novel objects. Time spent with the novel and moved objects in the E2-infused groups was significantly higher than that in the vehicle groups, independent of U0126 administration (#p < 0.05). Each bar represents the mean +/− SEM. Wendy A. Koss et al. eNeuro 2018;5:ENEURO.0267-18.2018 ©2018 by Society for Neuroscience