Effects of TAT-KLCpCDK peptide in animal models of depression and mania. (Ai) The GSK-3 inhibitor AR-A014418 and TAT-KLCpCDK both enhanced surface expression of GluR1 (AR control n = 5; AR-treated, n = 6, Student's t test, paired, P = 0.028; TAT-Con, n = 6, TAT-KLCpCDK, n = 8; Student's t test, unpaired, P = 0.014). (Aii) TAT-KLCpCDK infusion significantly reduced immobility time in the tail suspension test (one-way ANOVA, Bonferroni's multiple comparison test, n = 35, *P < 0.05). (Aiii) TAT-KLCpCDK infusion significantly reduced immobility time in the forced swim test (one-way ANOVA, Tukey's multiple comparison test, n = 55, *P < 0.01). (Bi) AR-A014418 blocked Sp-cAMP–induced insertion of GluR1 into the neuronal surface. Hippocampal neurons (12 DIV) were treated with AR-A014418 (10 μM) for 1 h and Sp-cAMP (50 μM) for an additional 30 min. A biotinylation assay was performed to determine surface GluR1 and GluR2 levels (one-way ANOVA, Bonferroni's multiple comparison test, N = 2, n = 40, **P < 0.001, *P < 0.05). (Bii) TAT-KLCpCDK peptide significantly inhibited AMPH-induced hyperactivity (repeated-measures ANOVA [F(1,13) = 11.4, P = 0.005]). (Biii) Time course of locomotor activity before or after AMPH. (Biv) Difference in distance traveled before and after AMPH (n = 7–8 animals per group, Student's t test, unpaired, two-tailed, *P = 0.005).