title: Preclinical assessment of CNS drug action using eye movements in mice.
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.
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Hugh
authors.initials: H
authors.lastname: Cahill
authors.forename: Amir
authors.initials: A
authors.lastname: Rattner
authors.forename: Jeremy
authors.initials: J
authors.lastname: Nathans
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects* / Q000502:physiology; D002491:Central Nervous System Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005133:Eye Movements / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009039:Motion Perception / Q000502:physiology; D017120:Nystagmus, Optokinetic / Q000187:drug effects / Q000502:physiology; D010775:Photic Stimulation; D045442:Rotarod Performance Test
chemical_list: D002491:Central Nervous System Agents