CB₁ and CB₂ receptors play differential roles in early zebrafish locomotor development

Endocannabinoids (eCBs) mediate their effects through actions on several receptors, including the cannabinoid receptors CB₁R and CB₂R. The role played by eCBs in the development of locomotor systems is not fully understood. In this study, we investigated the roles of the eCB system in zebrafish development by pharmacologically inhibiting CB₁R and CB₂R (with AM251 and AM630, respectively) in either the first or second day of development. We examined the morphology of motor neurons and we determined neuromuscular outputs by quantifying the amount of swimming in 5 days post-fertilization larvae. Blocking CB₂R during the first day of development resulted in gross morphological deficits and reductions in heart rate that were greater than those following treatment with the CB₁R blocker AM251. Blocking CB₁Rs from 0 to 24 h post-fertilization resulted in an increase in the number of secondary and tertiary branches of primary motor neurons, whereas blocking CB₂Rs had the opposite effect. Both treatments manifested in reduced levels of swimming. Additionally, blocking CB₁Rs resulted in greater instances of non-inflated and partially inflated swim bladders compared with AM630 treatment, suggesting that at least some of the deficits in locomotion may result from an inability to adjust buoyancy. Together, these findings indicate that the eCB system is pivotal to the development of the locomotor system in zebrafish, and that perturbations of the eCB system early in life may have detrimental effects.