Figure 4. Inhibition of the MEK/ERK pathway in the hippocampus has antidepressant properties in both wild-type and CRF2−/− mice in the forced swim test and tail suspension test.
Intrahippocampal (i.h.) administration of MEK inhibitor U0126 (250 μg/0.25 μl per side) 30 min before 12 min FST (Day 1) (a, b), or 6 min TST (d), reversed elevated depression-like behaviors of CRF2−/− mice and showed antidepressant-like properties in the wild-type mice. Locomotor activity as indicated by total distance travelled (cm) was not affected by i.h. U0126 (250 μg/0.25 μl per side) treatment (e). The number of animals per group in the FST and TST tests was 7 for CRF2 −/−, and 8 for CRF2+/+. For locomotor activity test, number of mice per group was 4. Different mice were used for separate tests. Representative blots (left), and mean ± SEM percent of pERK1 and pERK2 immunoreactivity (right) from hippocampal extracts taken from wild-type mice given i.h. infusions of 50% DMSO (vehicle) (n= 4 mice), or 1 μg/μl of U0126 (n= 4 mice) (a, b, d). The immunoblots were obtained from individual hippocampal lysates isolated 30 min after injection of inhibitor or vehicle. Normalized activated kinase levels in CRF2−/− mice were expressed as a percentage of those in wild-type mice (+/+) (c). Statistically significant differences: # p > 0.05 compared to vehicle treated mice of the same genotype; * p > 0.05 compared to vehicle treated wild-type littermates.