Figure 4. Administration of a selective M1-AChR antagonist produces antidepressant-like effects in the FST and increases mTORC1 signaling.
The influence of a selective M1-AChR antagonist, VU0255035 on immobility in the FST and mTORC1 signaling in the PFC was determined. (A) Rats were administered (i.p.) VU0255035 at two different doses, 1 and 3 mg/kg VU0255035 and 24 hr later were tested in the FST. We found that the 3 mg/kg dose of VU0255035 significantly decreased immobility in the FST (ANOVA and Newman-Keuls post hoc test). (B) For comparison, the influence of a M3-AChR antagonist, 4-DAMP, infused (i.c.v.) at two different doses was examined, but no significant effects were observed. (C) The influence of VU0255035 (3 mg/kg, i.p.) on mTORC1 signaling in the PFC was determined by western blot analysis. Shown on the right are representative immunoblots for each phosphorylated kinase, as well as total levels of the corresponding nonphosphorylated protein. Results are relative fold change and are the mean ± S.E.M., n = 7–9 per group. p < 0.05 compared to controls (Student’s t-test).