Figure 4
Genetic deletion of PDE11A in mice triggers alterations in the cAMP signaling pathway and increases sensitivity to the antidepressant and anti-manic effects of lithium. (a) Autoradiographic in situ hybridization shows that PDE11A KO mice exhibit a significant reduction in Arhgap32 mRNA specifically within ventral CA1 (VCA1) relative to wild-type (WT) littermates (n=9 per genotype), indicative of localized increases in pCREB signaling.51, 52 (b) PDE11A KO mice chronically fed 0.4% lithium chow (n=15), but not 0.2% lithium chow (n=21) demonstrated a significant antidepressant-like reduction in tail suspension test (TST) immobility relative to PDE11A KO mice fed a control diet (n=19). PDE11A WT and HT mice showed no significant change in immobility when fed either 0.4% (WT, n=16; HT, n=16) or 0.2% lithium chow (WT, n=20; HT, n=14) relative to the control diet (WT, n=18; HT, n=16). (c) At specific time points, PDE11A KO and PDE11A HT mice chronically fed the 0.4% lithium chow demonstrated a significant anti-manic-like attenuation of the amphetamine-stimulated rise in horizontal beam breaks relative to WT littermates (WT and HT, n=26; KO, n=25). Post hoc, #vs control chow, P=0.011; *vs KO, P=0.015-0.002; @vs HT, P=0.02. Data passed normality and equal variance and are graphed as means ±s.e.m. Brightness and contrast adjusted for graphical clarity of autoradiographic images. HT, heterozygous; KO, knockout; PDE11A, phosphodiesterase 11A.
