Figure 3.

Role of AMPA receptor and BDNF–TrkB signaling in the mechanisms of antidepressant effect for R-ketamine and S-ketamine. (a) The schedule of social defeat stress model and behavioral tests after treatment. NBQX (10 mg kg⁻¹), an AMPA receptor antagonist, was administered 30 min before saline, R-ketamine (10 mg kg⁻¹) or S-ketamine (10 mg kg⁻¹). Behavioral tests, including (b) LMT (one-way ANOVA, F_5,34=0.06, P=0.997), (c) TST (F_5,39=14.628, P<0.001) and (d) FST (F_5,42=9.015, P<0.001), were performed 1 day after a single dose. (e) SPT was 7 days after a single dose of saline, R-ketamine (10 mg kg⁻¹) or S-ketamine (10 mg kg⁻¹) (F_5,40=11.748, P<0.001). Values represent the mean±s.e.m. (n=6–9). *P<0.05, **P<0.01 and ***P<0.001. (f) The schedule of social defeat stress model and behavioral tests after treatment. ANA-12 (0.5 mg kg⁻¹), a TrkB antagonist, was co-administered with saline or R-ketamine (10 mg kg⁻¹) or S-ketamine (10 mg kg⁻¹). Behavioral tests, including (g) LMT (one-way ANOVA, F_5,37=0.414, P=0.836), (h) TST (F_5,33=14.044, P<0.001) and (i) FST (F_5,32=15.783, P<0.001), were performed 1 day after a single dose. (j) The SPT was 7 days after a single dose of saline, R-ketamine or S-ketamine (F_5,36=11.825, P<0.001). Values represent the mean±s.e.m. (n=6–8). *P<0.05, **P<0.01 and ***P<0.001. AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; ANOVA, analysis of variance; BDNF, brain-derived neurotrophic factor; FST, forced swimming test; LMT, locomotion test; N.S., not significant; SPT, sucrose preference test; TST, tail suspension test.