Brief exposure to (-) THC affects zebrafish embryonic locomotion with effects that persist into the next generation.

Cannabis is one of the most widely used drugs, and yet an understanding of its impact on the human brain and body is inconclusive. Medicinal and recreational use of cannabis has increased in the last decade with a concomitant increase in use by pregnant women. The major psychoactive compound in cannabis, Δ-tetrahydrocannabinol (THC), exists in different isomers, with the (-) trans isomer most common.

The endocannabinoid system's involvement in motor development relies on cannabinoid receptors, TRP channels, and Sonic Hedgehog signaling.

The endocannabinoid system (eCS) plays critical roles in locomotor function and motor development; however, the roles of non-canonical cannabinoid receptor systems such as transient receptor potential (TRP) channels and the Sonic Hedgehog (SHH) signaling pathway in conjunction with the eCS in sensorimotor development remains enigmatic. To investigate the involvement of canonical and non-canonical cannabinoid receptors, TRP channels, and the SHH pathway in the development of sensorimotor function in zebrafish, we treated developing animals with pharmacological inhibitors of the CB1R, CB2R, TRPA1/TRPV1/TRPM8, and a smoothened (SMO) agonist, along with inhibitors of the eCS catabolic enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) during the first ~24 h of zebrafish embryogenesis. Locomotor function was examined by assessing touch-evoked escape swimming at 2 days post-fertilization.

Inhibiting the endocannabinoid degrading enzymes FAAH and MAGL during zebrafish embryogenesis alters sensorimotor function.

The endocannabinoid system (eCS) plays a critical role in a variety of homeostatic and developmental processes. Although the eCS is known to be involved in motor and sensory function, the role of endocannabinoid (eCB) signaling in sensorimotor development remains to be fully understood. In this study, the catabolic enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) were inhibited either simultaneously or individually during the first ∼24 h of zebrafish embryogenesis, and the properties of contractile events and escape responses were studied in animals ranging in age from 1 day post-fertilization (dpf) to 10 weeks.