Fig. 1: The antidepressant-like effects of repeated or single treatment with rapastinel and changes in the expression of p-ERK, p-mTOR, and p-TrkB in mice.

A and B Experimental timeline schematic. C Repeated treatment with rapastinel significantly decreased the immobility time at 1, 7, and 14 days after withdraw of rapastinel. D However, single treatment with rapastinel significantly produced significant inhibition in immobility time only at 1 day after withdrawal of rapastinel. Our data indicated that repeated treatment with rapastinel induced the significant antidepressant-like effects in the FST of mice. However, single treatment with rapastinel induced antidepressant-like effects that only lasted a week. Based on our hypothesis about the VGF/BDNF/TrkB autoregulatory feedback loop and increase of ERK/mTOR signaling that may induce the significantly antidepressant-like actions, we performed western blotting to detect the levels of p-ERK, p-mTOR, and p-TrkB in the hippocampus and PFC of mice (E). Repeated treatment with rapastinel showed a significant increase in p-ERK (F), p-mTOR (G), and pTrkB (H) both in the hippocampus and PFC of mice after 14 days of withdrawal of rapastinel. However, the levels of these proteins were not changed by single treatment with rapastinel in the hippocampus and PFC of mice after 14 days of withdrawal of rapastinel. Data are expressed as means ± S.E.M; n = 10 per group for behavioral tasks and n = 5 per group for western blotting tests. *P < 0.05, **P < 0.01 compared with the vehicle group.