Evaluation of the role of NMDA receptor function in antidepressant-like activity. A new study with citalopram and fluoxetine in the forced swim test in mice

Pharmacol Rep. 2015 Jun;67(3):490-3. doi: 10.1016/j.pharep.2014.12.003. Epub 2014 Dec 17.

Abstract

Background: The NMDA/glutamate receptors are involved in the mechanism of antidepressant activity.

Methods: The present study was designed to investigate the effect of NMDA receptor ligands (agonists and antagonists of glutamate sites) on the antidepressant-like activity of selective serotonin reuptake inhibitors (SSRIs), citalopram and fluoxetine, in the forced swim test in mice.

Results: The antidepressant activity (reduction in immobility time) of citalopram but not of fluoxetine was antagonized by N-methyl-D-aspartate acid and enhanced by CGP37849 (antagonist of the NMDA receptor).

Conclusions: The present literature data indicate that the antidepressant-like activity of conventional antidepressants is generally affected by the NMDA receptor, although by modulation from different sites of the complex. Thus, it supports the issue of the ability of NMDA receptor antagonists to enhance the antidepressant action in human depression.

Keywords: CGP 37849; Citalopram; Fluoxetine; Forced swim test; NMDA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate / analogs & derivatives
  • 2-Amino-5-phosphonovalerate / pharmacology
  • Animals
  • Antidepressive Agents / therapeutic use*
  • Antidepressive Agents, Second-Generation / therapeutic use
  • Citalopram / therapeutic use*
  • Depression / drug therapy*
  • Depression / psychology
  • Drug Evaluation, Preclinical / methods
  • Fluoxetine / therapeutic use*
  • Male
  • Mice
  • Receptors, N-Methyl-D-Aspartate / agonists
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Swimming* / psychology

Substances

  • Antidepressive Agents
  • Antidepressive Agents, Second-Generation
  • Receptors, N-Methyl-D-Aspartate
  • Fluoxetine
  • Citalopram
  • 2-amino-4-methyl-5-phosphono-3-pentenoic acid
  • 2-Amino-5-phosphonovalerate