Drugs and drug administration

On the day of intraperitoneal injection a single dose of vehicle (10 ml/kg; 0.9% saline), MK-801 (0.1 mg/kg, Sigma-Aldrich; Merck KGaA, Darmstadt, Germany), and rapastinel (10 mg/kg, Tocris Bioscience, Bristol, UK) were administered to mice (Fig. 1A). Previously reported doses of MK-801 (0.1 mg/kg) and rapastinel (10 mg/kg) were used (7–9,11). If a drug exhibited antidepressant activity that lasted for >24 h in FST or 2 days in SPT mice, it was considered long-lasting (8,9).

Schedule of CUMS model, drug administration, behavioral tests and brain sampling. (A) CUMS was performed for 21 days. Stressed mice were used in the subsequent experiments. Vehicle, MK-801 (0.1 mg/kg), or rapastinel (10 mg/kg) was administered intraperitoneally (D22). LMT, TST and FST were performed 2, 4 and 8 h after injection of a single dose, respectively (D22-23). A 1% SPT test was performed 2 (D24) and 4 days (D26) after a single-dose injection. The collection of the brain regions was performed at D27. (B) LMT, (C) TST, (D) FST, and (E and F) 1% SPT results were determined. Values were presented as the mean ± standard error of the mean (10 mice/group). **P<0.01 and ***P<0.001 as indicated. Con, control; Veh, vehicle; MK, MK-801; Rap, rapastinel; CUMS, chronic unpredictable mild stress; LMT, locomotion test; TST, tail suspension test; FST, forced swim test; SPT, sucrose preference test; D, day; N.S., not significant.