Use of Zebrafish to Identify New CNS Drugs Acting Through Nicotinic and Dopaminergic Systems
Pp. 381-406 (26)
Robert T. Boyd
Zebrafish (Danio rerio) are a vertebrate animal model with advantages for
screening and development of therapeutic agents. The ease of growth and handling and the
ability of zebrafish to be treated with compounds in a multi-well format are advantages for
high-throughput screening (HTS) work to identify new drugs. Zebrafish have also been
used in target confirmation after a lead compound has been identified. In vivo structure
activity relationship (SAR) studies in zebrafish have also been performed. Indeed, zebrafish
can be used at several points in the drug discovery process. Zebrafish are ideal for testing
drug toxicity on a large scale, thus saving much time, money and effort to further develop a
compound with toxicity in vertebrates. Many behavioral assays developed in other animals,
and which are used to assay drugs targeted to several neurological diseases, are available in
zebrafish These include assays for locomotion, avoidance behaviors, learning, and
conditioned place preference. The use of zebrafish allows one to combine the ability to
perform behavioral assays with HTS and thus perform high-throughput in vivo drug
screening. Many biochemical pathways and genes present in humans are conserved in
zebrafish, including those involving the nicotinic cholinergic and dopaminergic systems.
Zebrafish is an exciting new system amenable to identification of new drugs to treat
disorders due to nicotinic cholinergic and dopaminergic disregulation including nicotine
addiction, schizophrenia, Alzheimer's disease and Parkinson's disease.
Department of Neuroscience, The Ohio State University College of Medicine, Wexner Medical Center, 333 West Tenth Avenue, Columbus Ohio 43210, USA.