TY - JOUR
T1 - Preclinical assessment of CNS drug action using eye movements in mice
AU - Cahill, Hugh
AU - Rattner, Amir
AU - Nathans, Jeremy
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2011/9/1
Y1 - 2011/9/1
N2 - The drug development process for CNS indications is hampered by a paucity of preclinical tests that accurately predict drug efficacy in humans. Here, we show that a wide variety of CNS-active drugs induce characteristic alterations in visual stimulus-induced and/or spontaneous eye movements in mice. Active compounds included sedatives and antipsychotic, antidepressant, and antiseizure drugs as well as drugs of abuse, such as cocaine, morphine, and phencyclidine. The use of quantitative eye-movement analysis was demonstrated by comparing it with the commonly used rotarod test of motor coordination and by using eye movements to monitor pharmacokinetics, blood-brain barrier penetration, drug-receptor interactions, heavy metal toxicity, pharmacologic treatment in a model of schizophrenia, and degenerative CNS disease. We conclude that eyemovement analysis could complement existing animal tests to improve preclinical drug development.
AB - The drug development process for CNS indications is hampered by a paucity of preclinical tests that accurately predict drug efficacy in humans. Here, we show that a wide variety of CNS-active drugs induce characteristic alterations in visual stimulus-induced and/or spontaneous eye movements in mice. Active compounds included sedatives and antipsychotic, antidepressant, and antiseizure drugs as well as drugs of abuse, such as cocaine, morphine, and phencyclidine. The use of quantitative eye-movement analysis was demonstrated by comparing it with the commonly used rotarod test of motor coordination and by using eye movements to monitor pharmacokinetics, blood-brain barrier penetration, drug-receptor interactions, heavy metal toxicity, pharmacologic treatment in a model of schizophrenia, and degenerative CNS disease. We conclude that eyemovement analysis could complement existing animal tests to improve preclinical drug development.
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U2 - 10.1172/JCI45557
DO - 10.1172/JCI45557
M3 - Article
C2 - 21821912
AN - SCOPUS:80052371082
VL - 121
SP - 3528
EP - 3541
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 9
ER -