Antidepressant Effects of (+)-MK-801 and (-)-MK-801 in the Social Defeat Stress Model

Abstract

Background: Current data on antidepressant action of the N-methyl-D-aspartate receptor antagonist, (+)-MK-801, is inconsistent. This study was conducted to examine the effects of (+)-MK-801 and its less potent stereoisomer, (-)-MK-801, in the social defeat stress model of depression.

Methods: The antidepressant effects of (+)-MK-801 (0.1mg/kg) and (-)-MK-801 (0.1mg/kg) in the social defeat stress model were examined.

Results: In the tail suspension and forced swimming tests, both stereoisomers significantly attenuated increased immobility time in susceptible mice. In the sucrose preference test, (+)-MK-801, but not (-)-MK-801, significantly enhanced reduced sucrose consumption 2 or 4 days after a single dose. However, no antianhedonia effects were detected 7 days after a single dose of either stereoisomer.

Conclusions: Both stereoisomers of MK-801 induced rapid antidepressant effects in the social defeat stress model, although neither produced a long-lasting effect (7 days).

Keywords: MK-801; NMDA receptor; antidepressant; ketamine; stereoisomer.

Figure 1.

The schedule of social defeat stress, drug administration, and behavioral tests. Repeated social defeat stress was performed for 10 days (day 1 to day 10). Social interaction test was performed day 11, and susceptible mice were used in the subsequent experiments. Vehicle, (+)-MK-801 (0.1mg/kg), or (-)-MK-801 (0.1mg/kg) was administered i.p. (day 12). Locomotion test (LMT) and tail suspension test (TST) were performed 4 and 6 hours after a single injection, respectively (day 12). Forced swimming test (FST) was performed 1 day after injection (day 13). A 1% sucrose preference test (SPT) was performed 2 days (day 14), 4 days (day 15), and 7 days (day 19) after a single injection.

Figure 2.

Antidepressant effects of (+)-MK-801 and (-)-MK-801 in social defeat stress model. Behavioral tests were performed as described in the Figure 1. A: LMT (day 12), B: TST (day 12), C: FST (day 13), D: SPT (day 14) E: SPT (day 16) and F: SPT (day 19). The values represent the mean ± SEM (n = 9 or 10). *P < .05, ** P < .01, *** P < .001 compared with the vehicle-treated stress group. Con: control; Veh: vehicle; (+)MK: (+)-MK-801; (-)MK: (-)-MK-801; LMT: locomotion test; TST: tail suspension test; FST: forced swimming test; SPT: 1% sucrose preference test.