Endocannabinoids in Zebrafish are Necessary for Normal Development and Locomotion

Author(s): Md Shah Sufian, Jayne Waldon, Richard Kanyo, W. Ted Allison and Declan W. Ali


Endocannabinoids (eCBs) are the primary endogenous agonists of the cannabinoid receptors CB1R and CB2R. eCBs are present from the very early stages of development but their actions are yet to be fully elucidated. In this study we sought to investigate the roles of the eCB system in zebrafish development by pharmacologically inhibiting the CB1 and CB2 receptors (with AM251 and AM630 respectively) prior to hatching. In these experiments we incubated embryos in AM251 or AM630 for the first 2 days of development. Treatment with either AM251 or AM630 resulted in embryos with axial malformations, shorter trunks, pericardial edema and reduced heart rates, particularly at higher concentrations at 2 dpf. Locomotion studies at 5 dpf revealed a change in their activity, swim velocity, the number of swim bouts and the cumulative duration of swim bouts. Together these findings indicate that the endocannabinoid system plays a significant role in the normal development of zebrafish, and that perturbations of the eCB system early in life have an impact on development.

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