TY - JOUR
T1 - Capturing the angel in angel dust
T2 - Twenty years of translational neuroscience studies of NMDA receptor antagonists in animals and humans
AU - Moghaddam, Bita
AU - Krystal, John H.
PY - 2012/9
Y1 - 2012/9
N2 - Here, we describe our collaborative efforts to use N-methyl-d-aspartate (NMDA) receptor antagonists as a translational tool to advance our understanding of the pathophysiology of schizophrenia and identify potential new targets for treatment of schizophrenia. We began these efforts in the late 1980s with a keen sense that, in both human and animal studies, we needed to move beyond the dopamine hypothesis of schizophrenia; if the dopamine hypothesis were correct, the existing dopamine antagonists should have cured the disease but they have not. We used NMDA receptor antagonists, not to produce schizophrenia, but as a tool to provide insights into effects of disturbances in glutamate synaptic function in schizophrenia. Our work has provided insights into potential mechanisms that may contribute to disrupted cortical function in schizophrenia and has helped identify potential treatment targets for the disorder. The translational nature of this study made the clinical testing of the first of these targets feasible. Advances in systems neuroscience approaches in animals and humans make new types of translational research possible; however, our concern is that the current obstacles facing translational research funding and academia-industry collaborations threaten the future progress in this field.
AB - Here, we describe our collaborative efforts to use N-methyl-d-aspartate (NMDA) receptor antagonists as a translational tool to advance our understanding of the pathophysiology of schizophrenia and identify potential new targets for treatment of schizophrenia. We began these efforts in the late 1980s with a keen sense that, in both human and animal studies, we needed to move beyond the dopamine hypothesis of schizophrenia; if the dopamine hypothesis were correct, the existing dopamine antagonists should have cured the disease but they have not. We used NMDA receptor antagonists, not to produce schizophrenia, but as a tool to provide insights into effects of disturbances in glutamate synaptic function in schizophrenia. Our work has provided insights into potential mechanisms that may contribute to disrupted cortical function in schizophrenia and has helped identify potential treatment targets for the disorder. The translational nature of this study made the clinical testing of the first of these targets feasible. Advances in systems neuroscience approaches in animals and humans make new types of translational research possible; however, our concern is that the current obstacles facing translational research funding and academia-industry collaborations threaten the future progress in this field.
KW - NMDA
KW - glutamate
KW - ketamine
UR - http://www.scopus.com/inward/record.url?scp=84866652398&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84866652398&partnerID=8YFLogxK
U2 - 10.1093/schbul/sbs075
DO - 10.1093/schbul/sbs075
M3 - Article
C2 - 22899397
AN - SCOPUS:84866652398
SN - 0586-7614
VL - 38
SP - 942
EP - 949
JO - Schizophrenia Bulletin
JF - Schizophrenia Bulletin
IS - 5
ER -