Fig. 1: Antidepressant effects of subanesthetic ketamine depend on NRG1/ErbB4 signaling.
A A schematic illustration of the forced swim test (FST) which was used to determine the dependence of the antidepressant effect of ketamine on NRG1/ErbB4 signaling. B Schematics for the experimental timelines (30 min or 24 h after treatment) for ketamine and HNK (left and right). C Wild-type mice were treated with saline (n = 7), ketamine (10 mg/kg; s.c.)(n = 8), or ketamine plus NRG1 (1 µg/mouse)(n = 9) and were then subjected to the FST 30 min later. Immobility times are shown (One-way ANOVA: overall p = 0.0069. Two-sample t test: ketamine + saline vs saline p = 0.0411, ketamine+NRG1 vs ketamine+saline p = 0.0066; mean ± SEM). D Wild-type mice were treated with saline (n = 10), ketamine (10 mg/kg; s.c.)(n = 10), or ketamine plus NRG1 (1 µg/mouse)(n = 10) and were subjected to the FST 24 hours later (One-way ANOVA: overall p = 0.0289. Two-sample t test: ketamine + saline vs saline p = 0.0257, ketamine + NRG1 vs ketamine+saline p = 0.0351; mean ± SEM). E Wild-type mice were treated with saline (n = 11), HNK (10 mg/kg; s.c.)(n = 14), or HNK plus NRG1 (1 µg/mouse)(n = 10) and were subjected to the FST 24 h later (One-way ANOVA: overall p = 0.0031. Two-sample t test: HNK + saline vs saline p = 0.0076, HNK + NRG1 vs HNK + saline p = 0.0071; mean ± SEM). F Control ErbB4fl/fl mice were treated with saline (n = 7) or ketamine (10 mg/kg; s.c.)(n = 8) and PV-Cre; ErbB4fl/fl mice were treated with saline (n = 9) or ketamine (10 mg/kg; s.c.)(n = 9) and tested on the FST 24 hours later (Two-way ANOVA: overall p = 0.0033. Two-sample t test: saline vs ketamine (ErbB4fl/fl) p = 0.0041, saline vs ketamine (PV-Cre; ErbB4fl/fl) p = n.s.; mean ± SEM). We find no significant effect of genotype. G Schematics for the experimental timelines for the ErbB4 antagonist PD158780. H Wild-type mice were treated with vehicle (n = 10) or PD158780 (10 mg/kg; s.c.) and subjected to the FST 30 min (n = 7), 2 h (n = 8) or 24 h (n = 6) later (One-way ANOVA: overall p = 0.0421. Two-sample t test: PD158780 vs saline, 30 min. p = n.s., 2 h p = 0.0098, 24 h p = 0.0395; mean ± SEM).
