Abstract
In this study, we investigated locomotor activity and responses to repeated light and dark stimuli to assess cannabinoid-induced abnormal behavior in zebrafish larvae (Danio rerio), as an alternative to standard rodent models. To induce the desired responses, we used cannabidiol and WIN55,212–2, two major cannabinoid components. A repeated light and dark test was used to assess how drug exposure influences locomotory responses. Larvae were examined after moderate cannabidiol and WIN55,212–2 exposure and at 24 h after transfer to untreated water. We found that cannabidiol did not produce a dose-dependent inhibitory effect on locomotor activity, with both 0.5 and 10 μg/mL concentrations reducing movement velocity and the total distance moved. However, 10 μg/mL cannabidiol was observed to attenuate the responses of larvae exposed to darkness. No differences were detected between the control and cannabidiol-treated groups after 24 h in fresh water. Fish treated with WIN55,212–2 at 0.5 and 1 μg/mL showed virtually no activity, even in darkness, whereas a concentration of 10 μg/mL induced mortality. A 24-h period in fresh water had the effect of reversing most of the drug-induced immobilization, even in the WIN55,212-2-treated groups. Larvae were also evaluated for their responses to cannabidiol subsequent to an initial exposure to WIN55,212–2, and it was accordingly found that treatment with cannabidiol could attenuate WIN55,212-2-induced abnormal immobilization, whereas equivalent doses of cannabidiol and WIN55,212–2 produced a mixed response. In conclusion, the behavioral effects of the two cannabinoids cannabidiol and WIN55,212–2 appear to be ratio dependent. Furthermore, the repeated light and dark test could serve as a suitable method for assaying drug-induced behavior.
Highlights
Cannabinoid is a generic term for compounds with a chemical structure derived from Cannabis sativa plants [1, 2], the behavioral effects of which have yet to be fully elucidated.Given the potential adverse effects of cannabis, the constituents that cause these side effects need to be identified
We evaluated the locomotion of zebrafish larvae during acute drug exposure and drug withdrawal, and, given that light sensitivity tests are common in rodent models, we examined whether repeated light or dark stimuli, as a measure of light sensitivity, would affect drug-induced locomotory responses
We found that responses to 0.5 μg/mL CBD differed significantly from those to 5 and 10 μg/mL, which can be attributed to the fact that locomotor activity, including that of control group larvae, tended to decrease during the 24-h withdrawal period, the motor activity of larvae exposed to high concentrations of CBD (5 and 10 μg/mL) did not show a significant reduction
Summary
Cannabinoid is a generic term for compounds with a chemical structure derived from Cannabis sativa plants [1, 2], the behavioral effects of which have yet to be fully elucidated. Given the potential adverse effects of cannabis, the constituents that cause these side effects need to be identified. In this regard, several assays have been developed that evaluate locomotor activities, startle latency, behavioral modification, and physiological conditions, including cardiac arrest [3,4,5]. Rodents are the preferred animal model for such studies, owing to their reliability in behavioral screenings, and predictable physiological responses [6,7,8].
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