Ketamine: NMDA Receptors and Beyond.
Human studies examining the effects of the dissociative anesthetic ketamine as a model for psychosis and as a rapidly acting antidepressant have spurred great interest in understanding ketamine's actions at molecular, cellular, and network levels. Although ketamine has unequivocal uncompetitive inhibitory effects on N-methyl-d-aspartate receptors (NMDARs) and may preferentially alter the function of NMDARs on interneurons, recent work has questioned whether block of NMDARs is critical for its mood enhancing actions. In this viewpoint, we examine the evolving literature on ketamine supporting NMDARs as important triggers for certain psychiatric effects and the possibility that the antidepressant trigger is unrelated to NMDARs. The rapidly evolving story of ketamine offers great hope for untangling and treating the biology of both depressive and psychotic illnesses.
Department of Psychiatry, Taylor Family Institute for Innovative Psychiatric Research, and Center for Brain Research in Mood Disorders, Washington University School of Medicine, St. Louis, Missouri 63110 zorumskc@wustl.edu.
Charles F
CF
Zorumski
Department of Psychiatry, Taylor Family Institute for Innovative Psychiatric Research, and Center for Brain Research in Mood Disorders, Washington University School of Medicine, St. Louis, Missouri 63110.
Yukitoshi
Y
Izumi
Department of Psychiatry, Taylor Family Institute for Innovative Psychiatric Research, and Center for Brain Research in Mood Disorders, Washington University School of Medicine, St. Louis, Missouri 63110.
Steven
0000-0003-0868-0664
S
Mennerick
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D019317:Evidence-Based Medicine; D006213:Hallucinogens; D006801:Humans; D007649:Ketamine; D011605:Psychoses, Substance-Induced / Q000209:etiology / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism*
D006213:Hallucinogens; C432823:NR2C NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine
antidepressant; hippocampus; ketamine; memantine; psychotomimetic