Analyzing cannabinoid-induced abnormal behavior in a zebrafish model

Abstract

This study investigated the locomotor activity and responses under stressful conditions to assess marijuana-induced abnormal behavior in zebrafish larvae (Danio rerio), as an alternative to the standard rodent model. To induce the desired symptoms, cannabidiol and WIN55,212-2, two chemical components derived from marijuana plants, were used. A repeated light and dark test was used to assess how drug exposure influenced locomotive responses. Subjects were examined after moderate cannabidiol and WIN55,212-2 exposure and 24 h after relocation into untreated water. Cannabidiol did not produce a dose-dependent inhibitory effect on locomotor activity; 0.5 and 10 μg/mL cannabidiol decreased total distance and velocity, and 10 μg/mL cannabidiol attenuated responses in the darkness. No differences between the control and cannabidiol-treated groups were apparent after 24 h in fresh water. WIN55,212-2 at 0.5 and 1 μg/mL almost completely stopped fish activity even in darkness and at 10 μg/mL induced mortality. Spending 24 h in fresh water almost reversed drug-induced immobilization, even in WIN55,212-2-treated groups. Subjects were evaluated for responses to additional cannabidiol after WIN55,212-2 exposure. Cannabidiol attenuated WIN55,212-2-induced abnormal immobilization, whereas commensurate doses of cannabidiol and WIN55,212-2 produced a mixed response. In conclusion, the behavioral effects of marijuana depend on the ratio of the two different cannabinoid properties. The repeated light and dark test might be a suitable method for drug-induced behavioral assay.