Capturing the angel in angel dust: Twenty years of translational neuroscience studies of NMDA receptor antagonists in animals and humans

Bita Moghaddam, John H. Krystal

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)942-949
Number of pages8
JournalSchizophrenia Bulletin
Volume38
Issue number5
DOIs
StatePublished - Sep 2012
Externally publishedYes

Fingerprint

Phencyclidine
Neurosciences
Schizophrenia
Translational Medical Research
Dopamine
Dopamine Antagonists
aspartic acid receptor
Glutamic Acid
Industry

Keywords

  • glutamate
  • ketamine
  • NMDA

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

@article{c338027b383b45faa516958ad8839648,
title = "Capturing the angel in angel dust: Twenty years of translational neuroscience studies of NMDA receptor antagonists in animals and humans",
abstract = "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.",
keywords = "glutamate, ketamine, NMDA",
author = "Bita Moghaddam and Krystal, {John H.}",
year = "2012",
month = "9",
doi = "10.1093/schbul/sbs075",
language = "English (US)",
volume = "38",
pages = "942--949",
journal = "Schizophrenia Bulletin",
issn = "0586-7614",
publisher = "Oxford University Press",
number = "5",

}

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 - glutamate

KW - ketamine

KW - NMDA

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

VL - 38

SP - 942

EP - 949

JO - Schizophrenia Bulletin

JF - Schizophrenia Bulletin

SN - 0586-7614

IS - 5

ER -