Use of Zebrafish to Identify New CNS Drugs Acting Through Nicotinic and Dopaminergic Systems

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.