Date of Award
Epileptic disorders like Dravet Syndrome require novel studies to determine the most ideal treatment. New research linking the endocannabinoid system (ECS) to epileptic disorders is arising, but there is still much to be discovered about the function and regulatory impact of the endocannabinoid system and its receptors in epilepsies like Dravet. In this study, knockout models of larval and adult zebrafish (Danio rerio) were used to investigate the roles of cannabinoid receptors 1 & 2 in behavior, brain mitochondrial metabolism, and seizure-induced activity following exposure to THC and CBD. Larval zebrafish which lacked cannabinoid receptor 1 exhibited increased locomotion compared to the wild-type (5D) line and cannabinoid receptor 2 null line. Conversely, adult zebrafish which lacked cannabinoid receptor 1 exhibited decreased locomotion, while adult zebrafish which lacked cannabinoid receptor 2 exhibited increased time spent in the periphery in the open field test compared to the wild-type line. Adult males significantly spent more time in the periphery than females and exhibited higher metabolic rates during specific stages of mitochondrial respiration regardless of line. Larval zebrafish that were exposed to THC and CBD following seizure induction by pentylenetetrazole (PTZ) were unaffected by the cannabinoid treatment, displaying no significant response. While we could not determine the exact mechanism behind the function of cannabinoid receptors in seizure-induced activity, this study found that cannabinoid receptors 1 & 2 do play a role in the behavior of zebrafish and are possibly involved in pathways that may link the ECS to epileptic behavior.
Kimmons, Kayci, "Characterizing the roles of cannabinoid receptor 1 & 2 in zebrafish behavior, metabolism, and seizure-induced activity" (2022). Honors Theses. 2530.
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