Fig. 5

Fig. 5

Amoxapine results from different assays. A Dose–response curve of amoxapine derived from TEVC recordings in X. laevis oocytes expressing α1β3γ2 concatenated GABA_AR. Representative traces depicted on the right. Data depict mean ± SEM. B Mean (± SEM) concentration–response data summary of amoxapine (3, 10, 30, and 100 μM) effects on CA1 population spike area in rat hippocampal brain slices. Statistical testing was run on raw concentration data (dose: F_(4,36) = 22.85, p < .001; Dunnett’s post hoc: amoxapine 30 μM vs veh, p < .05; amoxapine 100 μM vs veh, p < .001). C Calcium oscillation evaluation showing the average of the amoxapine concentration effect on frequency then on amplitude (values depict % of vehicle ratio) and a sample traces recordings for vehicle and amoxapine for the highest amoxapine concentration, namely, 30 µM. D Microelectrode array (MEA) recordings from rat cortical neurons. E Microelectrode array (MEA) recordings with human iPS glutamatergic neurons in co-culture with human astrocytes. The values in the heat maps (D, E) are presented as maximum percentage of change vs baseline after a treatment duration of 1 h (D) or 10 min (E). Each value represents the mean of 3 (D) or 5 (E) wells. A red color shows an increase of the respective endpoint, while a green color shows a decrease of the respective endpoint value compared to baseline (0%). The intensity of the colors indicates the magnitude of the effects as shown below. F–I Effect of amoxapine treatment on zebrafish larvae locomotor measurements during 1-h exposure period using video-tracking system (n = 8 larvae/group): F Total distance moved in mm (TDM), median ± median absolute deviation (mad); *p ≤ 0.05, **p ≤ 0.01, and ***p ≤ 0.001 versus control group (2-way ANOVA type with repeated measure on factor time); G total distance moved at high velocity(> 20 mm/s) (TDMH) in mm median ± mad; *p ≤ 0.05, **p ≤ 0.01, and ***p ≤ 0.001 versus control group (2-way ANOVA type with repeated measure on factor time); H frequency at high velocity (> 20 mm/s) (FH), median ± mad; *p ≤ 0.05, **p ≤ 0.01, and ***p ≤ 0.001 versus control group (2-way ANOVA type with repeated measure on factor time); I maximal velocity (MV) in mm/s, median ± mad; **p ≤ 0.01 versus control group (Dunnett’s test after transformation on rank)