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

Abstract

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 the CB1R and CB2Rs (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 dpf larva. Blocking CB2R during the first day of development resulted in gross morphological deficits and reductions in heart rate that were greater than that following treatment with the CB1R blocker AM251. Blocking CB1Rs from 0 to 24 hpf 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, suggesting that at least some of the deficits in locomotion may result from an inability to adjust buoyancy. Together these findings indicate that the endocannabinoid 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.