Antidepressant Effects of (+)-MK-801 and (-)-MK-801 in the Social Defeat Stress Model.
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.



The antidepressant effects of (+)-MK-801 (0.1mg/kg) and (-)-MK-801 (0.1mg/kg) in the social defeat stress model were examined.



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.



Both stereoisomers of MK-801 induced rapid antidepressant effects in the social defeat stress model, although neither produced a long-lasting effect (7 days).
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan (Dr Yang, Dr Ren, Ms Ma, and Dr Hashimoto); Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China (Drs Yang and Chen).
Bangkun
B
Yang
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan (Dr Yang, Dr Ren, Ms Ma, and Dr Hashimoto); Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China (Drs Yang and Chen).
Qian
Q
Ren
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan (Dr Yang, Dr Ren, Ms Ma, and Dr Hashimoto); Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China (Drs Yang and Chen).
Min
M
Ma
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan (Dr Yang, Dr Ren, Ms Ma, and Dr Hashimoto); Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China (Drs Yang and Chen).
Qian-Xue
QX
Chen
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan (Dr Yang, Dr Ren, Ms Ma, and Dr Hashimoto); Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China (Drs Yang and Chen). hashimoto@faculty.chiba-u.jp.
Kenji
K
Hashimoto
D000374:Aggression; D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D019422:Dietary Sucrose / Q000008:administration & dosage; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000737:chemistry / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects; D019417:Hindlimb Suspension; D008297:Male; D008810:Mice, Inbred C57BL; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012919:Social Behavior; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013550:Swimming; D013997:Time Factors
D000928:Antidepressive Agents; D019422:Dietary Sucrose; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate
MK-801; NMDA receptor; antidepressant; ketamine; stereoisomer