Role of NMDA Antagonists in Animal Models of Depression


  • Prabhakar Adake Assistant Professor of Pharmacology, Yenepoya Medical College, Mangalore, Karnataka.
  • Mahalaxmi S. Petimani Assistant Professor of Biochemistry, Yenepoya Medical College, Mangalore, Karnataka.


Amantidine, Forced swim test, Imipramine, NMDA antagonists, Tail suspension test


Background: The glutamate system has been studied in depression recently. This is a different from our previous thinking, which had only focused on the levels of serotonin and norepinephrine. The glutamate system may represent a new platform for the management of depression. NMDA and AMPA are receptors for excitatory neurotransmitter, glutamate. Blocking NMDA increases the activity of another receptor, AMPA and this enhanced AMPA activity is cause for rapid antidepressant action. Amantidine and ketamine being non-competitive antagonists of NMDA receptor is evaluated for their antidepressant activity in this study.

Objectives: The objective of the study was to evaluate the antidepressant activity of NMDA antagonists, amantidine and ketamine in Swiss albino mice.

Methodology: Total of 48 (n=48) Swiss albino male mice were used. They were divided into eight groups of six mice in each group. First four groups received, normal saline 10mg/kg (control), imipramine 10mg/kg (standard) and amantidine 30 mg/kg (test drug-1) and ketamine 50mg/kg (test drug-2) per orally and evaluated for antidepressant activity by tail suspension test (TST) after sixty minutes of oral drug administration. Similarly, remaining four groups received the same drugs and evaluated for antidepressant action by forced swim test (FST) after sixty minutes of oral drug administration. Duration of immobility was observed for 6 minutes in tail suspension test and for 4 minutes in forced swim test for each mouse.

Results: Results were analyzed by ANOVA followed by Post hoc Tukey’s test. The mean immobility time for TST and FST after the administration of amantidine (30 mg/kg) was found to be 77.33± 15.05 and 95.17± 20.07 seconds respectively. Similarly, for ketamine (50mg/kg), the mean immobility time was 160.00±26.79 and 117.2±21.8 seconds respectively for TST and FST models. The amantidine and ketamine significantly reduced the immobility time in both the models of depression when compared to control (p < 0.05).

Conclusion: Non-competitive antagonists, amantidine and ketamine have significant antidepressant activity in acute models of depression.


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