EFFECT OF NMDA RECEPTOR ANTAGONISTS IN FORCED SWIMMING TEST AND ITS MODIFICATION BY ANTIDEPRESSANTS

Objective: To investigate the antidepressant effect of NMDA receptor (NMDAR) antagonists (MK 801 and ketamine) using forced swimmming test, and to study their interaction with established antidepressants. Methods: The study was conducted in albino mice of either sex weighing 25±5g. They were subjected to forced swimming test. The duration of immobility of mice in the last 4 min of a 6min test was recorded. A mouse was considered immobile when floating motionless, or making only those movements necessary to keep its head above water. All the drugs were dissolved in 0.9% saline and were administered intraperitoneally. The data was analysed using ANOVA followed by either Dunnett's test or Tukey's multiple range test, wherever applicable. Results: Imipramine (8-32 mg/kg), MK 801 (0.05-0.2 mg/kg) and ketamine (2.5-10 mg/kg) reduced duration of immobility in a dose dependent fashion. The immobility reducing effect of imipramine (16 mg/ kg) was potentiated by concomitant administration of either MK 801 (0.1 mg/kg) or ketamine (5 mg/kg). Fluvoxamine (5-20 mg/kg) failed to modify the duration of immobility. However, fluvoxamine (20 mg/kg) potentiated the immobility reducing action of MK 801 (0.1 mg/kg) and ketamine (5 mg/kg). The positive response of imipramine was antagonised by prazosin (3 mg/kg), whereas that of MK 801 and ketamine was abolished by haloperidol (0.1 mg/kg). Haloperidol could also antagonise the effect of the combination of fluvoxamine with NMDA antagonists. Both prazosin and haloperidol pretreatment attenuated the effect of the combination of NMDA antagonists with imipramine. Conclusion: MK 801 and ketamine reduced the duration of immobility which was antagonised by haloperidol pretreatment. This suggests that antidepressant action of these agents is mediated through dopaminergic pathway. Both these agents also potentiated the actions of imipramine and fluvoxamine.