Figure 5.

The antidepressant-like actions of ketamine are mediated through GluN2A activity. A, Mice received an injection of vehicle or the GluN2A-selective NMDAR negative allosteric modulator PEAQX (5 or 30 mg/kg) followed by an injection of vehicle or ketamine (10 mg/kg) 10 min later, and then were tested for reversal of helpless behavior 24 h later. PEAQX pretreatment, at both doses administered, prevented the antidepressant-relevant actions of ketamine to decrease escape failures of helpless mice. B, The GluN2A-selective NMDAR positive allosteric modulator GNE-5729 induced a decrease in locomotor activity of mice in the open-field test only at the highest dose administered (3 mg/kg). C, In the forced-swim test, GNE-5729 at the dose of 3 mg/kg significantly reduced immobility time of mice, indicative of an antidepressant response. D, Similarly, the dose of 1 mg/kg of GNE-5729 significantly reduced escape failures of helpless mice. Data are the mean ± SEM; *p < 0.05, ***p < 0.001 as indicated by Holm–Šídák post hoc comparisons. See Table 1 for complete details on the statistical analyses and precise group sizes. KET, ketamine; SAL, saline; VEH, vehicle.