Journal
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
Volume 19, Issue 12, Pages -Publisher
OXFORD UNIV PRESS
DOI: 10.1093/ijnp/pyw080
Keywords
antidepressant; ketamine; MK-801; NMDA receptor; stereoisomer
Funding
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- Japan Agency for Medical Research and development, AMED
- China Scholarship Council
- Research Fellowship of the Japan Society for the Promotion of Science (Tokyo, Japan)
- Nurture of Creative Research Leaders in Immune System Regulation and Innovative Therapeutics Program of Chiba University
- Grants-in-Aid for Scientific Research [15J00058] Funding Source: KAKEN
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Background: Current data on antidepressant action of the N-methyl-D-aspartate receptor antagonist, (+)-MK-801, is inconsistent. This study was conducted to examine the effects of (+)-MK-801 and its less potent stereoisomer, (-)-MK-801, in the social defeat stress model of depression. Methods: The antidepressant effects of (+)-MK-801 (0.1 mg/kg) and (-)-MK-801 (0.1 mg/kg) in the social defeat stress model were examined. Results: In the tail suspension and forced swimming tests, both stereoisomers significantly attenuated increased immobility time in susceptible mice. In the sucrose preference test, (+)-MK-801, but not (-)-MK-801, significantly enhanced reduced sucrose consumption 2 or 4 days after a single dose. However, no antianhedonia effects were detected 7 days after a single dose of either stereoisomer. Conclusions: Both stereoisomers of MK-801 induced rapid antidepressant effects in the social defeat stress model, although neither produced a long-lasting effect (7 days).
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