Journal
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
Volume 21, Issue 10, Pages 932-937Publisher
OXFORD UNIV PRESS
DOI: 10.1093/ijnp/pyy053
Keywords
(2R,6R)-hydroxynorketamine; (R)-ketamine; sex-specific difference
Funding
- Strategic Research Program for Brain Sciences from Japan Agency for Medical Research and Development, AMED [JP17dm0107119]
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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.
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