Fig. 1: pCREB and PER2 levels in the CA1 region of the hippocampus are decreased in the ouabain-induced mania model.

A Experimental design of the ouabain model and behavioral analyses: the rats are i.c.v. infused (day0) with aCSF or ouabain (Oua), daily i.p. injected (day1–7) with saline or lithium carbonate (Li), behaviorally tested (day5–7) and sacrificed for brain tissue harvesting. The effects of aCSF (control)/Oua infusion and the following saline/Li treatment (n = 9 rats per group) on sucrose preference (B) in sucrose preference test (SPT) and immobility time (C) in forced swim test (FST). D Representative images of rat traces in the elevated plus maze test (EPM). Effects of Oua and Li on the number of entries (E) and time spent (F) in the open arms of EPM test. G Representative images of rat traces in the in the open field test (OFT). Effects of Oua and Li on total distance traveled (H) and time spent in the central zones (I) of the OFT. J Representative western blots showing PER2, pCREB and CREB protein expression in CA1 area at ZT02. Quantification of relative PER2 protein levels normalized to GAPDH (K) and pCREB:CREB ratio (L) (n = 3 rats per group). Two-way ANOVA with Tukey’s post-hoc test: *P < 0.05, **P < 0.01, ***P < 0.001 vs. control + vehicle group; #P < 0.05, ##P < 0.01 vs. ouabain + vehicle group). Data are presented as mean ± SEM and the individual data points are depicted. See also Supplementary Fig. S1 and Supplementary Table S1. Some of the sketches were made with biorender.com.