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Published in

American Society for Clinical Investigation, Journal of Clinical Investigation, 9(121), p. 3528-3541, 2011

DOI: 10.1172/jci45557

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Preclinical assessment of CNS drug action using eye movements in mice

Journal article published in 2011 by Hugh Cahill, Amir Rattner ORCID, Jeremy Nathans
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Preprint: archiving forbidden
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Postprint: archiving forbidden
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Published version: archiving allowed
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Abstract

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 eye-movement analysis could complement existing animal tests to improve preclinical drug development.