Zebrafish Conditioned Place Preference Models of Drug Reinforcement and Relapse to Drug Seeking

This protocol details simple zebrafish conditioned place preference assays for assessing reinforcing properties of drugs of abuse such as ethanol, which can be administered to the tank water. We further describe a conditioned place preference assay of stimulus-induced reinstatement of drug-seeking in zebrafish. The test apparatus consists of a 1.5 L tank that can be divided into two compartments using a Perspex divider and environmental cues that can be placed around the tank. Drug exposure is paired with visual environmental cues at either end of the tank, and a change in preference towards the drug-paired end is taken as indicative of a reinforcing effect of the drug. Using the treatment paradigm described, a 30–50% ethanol-induced change in place preference is observed. Following extinction, this place preference can be reinstated by low-dose, non-contingent ethanol exposure. The simple procedures described here can be used to gain insight into genetic mechanisms contributing to vulnerability to drug dependence and addiction.