title: Antipsychotics produce locomotor impairment in larval zebrafish.
abstract: Zebrafish has been a favored vertebrate genetic model organism for studying developmental processes. It also holds a great potential for understanding the genetic basis of behavior and associated behavioral disorders. Despite such potential, their use in the study of behavior is greatly under-explored. It is well known that multiple classes of drugs used to treat psychiatric diseases produce extrapyramidal side (EPS) effects and consequent movement disorders in humans. The underlying molecular causes of these drug-induced movement disorders are poorly understood. Here we report that zebrafish treated with the antipsychotics fluphenazine and haloperidol (both of which can induce severe EPS in humans) develop movement defects. In contrast, another antipsychotic olanzapine, which produces mild to little EPS in humans, leads to minimal movement defects in zebrafish. These results establish a rapid assay system in which the effects of EPS-inducing agents can be assessed. Thus, future genetic screening in zebrafish shall identify genes and pathways that elucidate drug-induced movement disorder in human as well as provide insights into the brain control of locomotor activity. Future chemical screening in zebrafish may act as a preclinical test for the EPS effect of certain drugs, as well as a test used to researching drugs made to counteract the effects of EPS.
authors.affiliation: Department of Biopharmaceutical Sciences, Programs in Human Genetics and Biological Sciences, University of California, San Francisco, California, 94143-0446, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Giacomini
authors.forename: Brian
authors.initials: B
authors.lastname: Rose
authors.forename: Kayta
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Su
authors.initials: S
authors.lastname: Guo
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004347:Drug Interactions; D005476:Fluphenazine / Q000633:toxicity*; D006220:Haloperidol / Q000633:toxicity*; D007814:Larva / Q000187:drug effects; D007980:Levodopa / Q000627:therapeutic use; D009043:Motor Activity / Q000187:drug effects*; D009069:Movement Disorders / Q000188:drug therapy / Q000209:etiology*; D013550:Swimming; D015027:Zebrafish
chemical_list: D000978:Antiparkinson Agents; D014150:Antipsychotic Agents; D007980:Levodopa; D006220:Haloperidol; D005476:Fluphenazine