Early application of CBD and THC reduce subsequent neural activity and locomotor activity. (a) The chemical structures of key cannabinoids used in this study: CBD and THC. (b), Timeline of experimental set up where zebrafish embryos were treated with drugs between 0.5 and 1 h post-fertilization (hpf) and washed out at 10 hpf towards the end of gastrulation. CaMPARI imaging was obtained at 4 days post-fertilization (dpf) and locomotor activity was tracked at 5 dpf. (c) and (f), Representative CaMPARI activity maps obtained from treated larvae and corresponding quantification and statistics shown in (d) and (g), respectively. (e) and (h), Locomotor activity of the same larvae. (c) CBD reduces neural activity and locomotor activity as shown in (d) and (e). (f) THC requires a higher does than CBD to reduce neural activity and locomotor activity as shown in (g) and (h). CaMPARI activity heat maps show ratio of R/G channels as indicated by the calibration bar, with higher ratios (hotter colours) representing greater neural activity. Green-dashed lines depict mean baseline (zero) value for MS-222 anesthetized samples (From Fig. 1). Biological replicates are n = 8–19. *is p < 0.05; **p < 0.01 compared to the vehicle control (0.3% MeOH in experiments with CBD and 0.6% MeOH for THC).
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