Role of NMDA receptor GluN2D subunit in the antidepressant effects of enantiomers of ketamine

J Pharmacol Sci. 2017 Nov;135(3):138-140. doi: 10.1016/j.jphs.2017.11.001. Epub 2017 Nov 10.

Abstract

We investigated the rapid and sustained antidepressant effects of enantiomers of ketamine in N-methyl-d-aspartate (NMDA) receptor GluN2D subunit knockout (GluN2D-KO) mice. Intraperitoneal administration of ketamine or its enantiomers 10 min before the tail-suspension test exerted significant antidepressant effects on restraint stress-induced depression in both wildtype and GluN2D-KO mice. The antidepressant effects of (RS)-ketamine and (S)-ketamine were sustained 96 h after the injection in both wildtype and GluN2D-KO mice, but such sustained antidepressant effects of (R)-ketamine were only observed in wildtype mice. These data suggest that the GluN2D subunit is critical for the sustained antidepressant effects of (R)-ketamine.

Keywords: Depression; GluN2D; Ketamine.

MeSH terms

  • Animals
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents / therapeutic use
  • Depression / drug therapy
  • Injections, Intraperitoneal
  • Ketamine / administration & dosage
  • Ketamine / pharmacology*
  • Ketamine / therapeutic use
  • Mice, Inbred C57BL
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Stereoisomerism

Substances

  • Antidepressive Agents
  • NR2D NMDA receptor
  • Receptors, N-Methyl-D-Aspartate
  • Ketamine