Fig. 4.

Pharmacological inhibition of MNK1/2 induces despair-like behavior and 5-HT synaptic impairments. a Cercosporamide, an MNK1 and MNK2 inhibitor, was administered for 5 consecutive days to wild-type mice (IP, 20 mg kg⁻¹). b Representative western blot images for phosphorylated eIF4E (p-eIF4E), total eIF4E and GAPDH in the cortex-hippocampus of mice treated with vehicle or cercosporamide. c Average levels of p-eIF4E in vehicle and cercosporamide-treated wild-type mice (vehicle (0 mg kg⁻¹), n = 7; cercosporamide, n = 7). d Cercosporamide administration induced increased immobility in the Forced Swim Test (FST) in wild-type mice (vehicle (0 mg kg⁻¹), n = 8; cercosporamide, n = 7). e Representative sEPSC traces from recordings in layer V mPFC from wild-type or Eif4e ki/ki mice treated with vehicle or cercosporamide. f Layer V mPFC sEPSC frequency of wild-type (left panel, vehicle n = 5 neurons from three mice, cercosporamide n = 6 neurons from two mice) or Eif4e ki/ki mice (right panel, vehicle n = 5 neurons from 2 mice, cercosporamide n = 7 neurons from 3 mice) treated with vehicle or cercosporamide. g Firing rate of 5-HT DR neurons in wild-type and Eif4e ki/ki mice treated with vehicle or cercosporamide (Eif4e^+/+: Vehicle 33 neurons from 6 mice, cercosporamide 22 neurons from 10 mice; Eif4e ki/ki: vehicle 22 neurons from 4 mice, cercosporamide 18 neurons from 4 mice). * p < 0.05, ** p < 0.01, ***p < 0.001 vs vehicle-treated wild-type mice; & p < 0.05 vs. saline-treated Eif4e^+/+ (see Supplementary Table 2 for detailed results of statistical tests)