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 CB 1 R and CB 2 R. 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 CB 1 R and CB 2 R (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 postfertilization larvae. Blocking CB 2 R 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 CB 1 R blocker AM251. Blocking CB 1 Rs 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 CB 2 Rs had the opposite effect. Both treatments manifested in reduced levels of swimming. Additionally, blocking CB 1 Rs 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.

Medium-throughput zebrafish optogenetic platform identifies deficits in subsequent neural activity following brief early exposure to cannabidiol and Δ-9-tetrahydrocannabinol

“…Using HEK cells several receptor candidates have been identified showing to interact with CBD 25 . A recent study supports a functional role of CB1R and CB2R in zebrafish 32 . Here, by inhibiting CB1R, and CB2R, we found that the reduction in locomotor activity mediated by CBD was partially prevented at nanomolar concentrations of the inhibitors.…”

“…Translucent larvae provide opportunities to implement cutting-edge fluorescing calcium sensors and measure neural activity. Past studies suggest that the endocannabinoid system plays a role in zebrafish development 30–32 . In addition, both cannabinoid receptors investigated here have similar expression profiles in the CNS compared to mammals, with CB1R sharing a 70 % protein sequence identity with the human homolog 33 .…”

Medium-throughput zebrafish optogenetic platform identifies deficits in subsequent neural activity following brief early exposure to cannabidiol and Δ9-tetrahydrocannabinol

“…Translucent larvae provide opportunities to implement cutting-edge fluorescing calcium sensors and to measure neural activity. The endocannabinoid system plays a role in zebrafish development 30 – 32 . CB1R and CB2R have similar expression profiles in the CNS of zebrafish compared to mammals, and CB1R shares a 70% protein sequence identity with its human homolog 33 .…”

Cannabinoid Receptors: An Update on Cell Signaling, Pathophysiological Roles and Therapeutic Opportunities in Neurological, Cardiovascular, and Inflammatory Diseases

“…While both CB1R and CB2R transcripts were identified in the human trophoblast during the first trimester, in vitro experiments demonstrated that anandamide prevented the proliferation of BeWo trophoblast cells via the CB2R [ 227 ]. In a recent study using zebrafish embryos, it was demonstrated that blocking CB2Rs during early development resulted in a greater inhibition of heart rate than that observed with a CB1R blocker [ 228 ]. Additionally, both CB1Rs and CB2Rs were also reported in embryonic stem cells (ESC) [ 229 , 230 ].…”