No Sex-Specific Differences in the Acute Antidepressant Actions of (R)-Ketamine in an Inflammation Model

Int J Neuropsychopharmacol. 2018 Oct 1;21(10):932-937. doi: 10.1093/ijnp/pyy053.

Abstract

Background: Although previous reports suggest sex-specific differences in the antidepressant actions of (R,S)-ketamine, these differences in the antidepressant actions of (R)-ketamine, which is more potent than (S)-ketamine, are unknown.

Methods: Saline or (R)-ketamine was administered 23 hours post lipopolysaccharide administration to adult male or female mice. Subsequently, antidepressant effects were assessed using a forced swimming test. Furthermore, the concentration of (R)-ketamine and its 2 major metabolites, (R)-norketamine and (2R,6R)-hydroxynorketamine, was measured in the plasma and brain after the administration of (R)-ketamine in the mice.

Results: (R)-ketamine (10 mg/kg) significantly attenuated the increased immobility time of forced swimming test in the lipopolysaccharide-treated mice. There were no sex-specific differences in the concentrations of (R)-ketamine and its 2 metabolites in the plasma and brain.

Conclusions: These findings showed no sex-specific differences in terms of the acute antidepressant effects and pharmacokinetic profile of (R)-ketamine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Female
  • Immobility Response, Tonic / drug effects*
  • Inflammation / chemically induced
  • Inflammation / psychology*
  • Ketamine / analogs & derivatives
  • Ketamine / blood
  • Ketamine / pharmacokinetics*
  • Ketamine / pharmacology*
  • Lipopolysaccharides
  • Male
  • Mice
  • Sex Characteristics
  • Stereoisomerism

Substances

  • Lipopolysaccharides
  • Ketamine