Figure 4. Stimulation of phospho-ERK by rapid-acting antidepressants requires AMPA and TrkB receptors.
(a–c) Cultured neurons were incubated with 50 µM NBQX 20 min prior to addition of ketamine (a, 500 nM), LY341496 (b, 10 nM), or GLYX-13 (c, 3 nM), all for 1 hr incubation. Pretreatment with NBQX completely blocked the induction of pERK (pERK) activation by all three agents. NBQX alone did not have an effect on pERK activation (a). (d-f) Cultures were incubated with 500 nM K252a for 20 min prior to addition of ketamine (d), LY341496 (e), or GLYX-13 (f), all for 1 hr incubation. Pretreatment with K252a blocked the induction of pERK by all three agents. K252a alone did not have an effect on pERK activation (d). Levels of total ERK and S6K were determined to control for gel loading and membrane transfer. Results are presented as mean ± SEM. *p < 0.05, **p < 0.005, ***p < 0.0005 compared to vehicle or blockade (ANOVA and Fisher’s post-hoc least significant difference test for results).