Behavioral screening for cocaine sensitivity in mutagenized zebrafish

TLDR

Forward genetic manipulation can expand the list of candidate genes for addiction. Zebrafish exhibit cocaine‑induced conditioned place preference, and a pilot screen of 18 F₂ families identified three with dominantly inherited low responses, with secondary screens indicating distinct gene mutations affecting dopaminergic signaling in retina and brain.

Abstract

Understanding the molecular basis of addiction could be greatly aided by using forward genetic manipulation to lengthen the list of candidate genes involved in this complex process. Here, we report that zebrafish exhibit cocaine-induced conditioned place preference. In a pilot screen of 18 F 2 generation families of mutagenized fish, we found three with abnormally low responses to cocaine. This behavior was inherited by the F 3 generation in a manner that suggests the abnormalities were because of dominant mutations in single genes. Performance profiles in secondary behavioral screens measuring visual dark-adaptation and learning suggest that the defects were the result of mutations in distinct genes that affect dopaminergic signaling in the retina and brain.