Early Life Δ9-Tetrahydrocannabinol Exposure of F0 Zebrafish Causes Hyperactivity in F1 Offspring

As cannabis increases in its accessibility, potency, and acceptance across the United States, investigation into the multigenerational effects of Δ9-tetrahydrocannabinol (THC) exposure during key stages of development is critical. The aim of this study was to evaluate whether there would be behavioral impacts in the F1 offspring following a dose-response of THC exposure (0.08, 0.4, or 1 µM) during development in the F0 generation. Zebrafish (Danio rerio) were utilized in this study. Behaviors (locomotive activity and anxiety-like behavior) in the F1 generation were evaluated at 120 hours post-fertilization (hpf) with the larval photometer response (LPR) assay, and at 3, 11, and 24 weeks post-fertilization (wpf) in an open field test (OFT). F1 zebrafish at 120 hpf showed hyperactivity compared to controls in the dark-phase of the LPR assay following F0 exposure to 0.4 and 1 μM THC. In the OFT at 3 wpf, velocity, freezing duration, and time spent in the periphery were not significantly altered compared to controls. At 11 wpf, freezing duration, but not velocity or time spent in the periphery, was significantly increased following parental 0.4 µM THC exposure. At 24 wpf, velocity was significantly increased in the F1 males whose parents were developmentally exposed to 0.08 and 1 µM THC compared to controls. Time spent in the periphery and freezing duration was not significantly altered in F1 males or females at 24 wpf. These results suggest that exposure to cannabis during critical periods of development have multigenerational physiological implications for F1 generations that persist in zebrafish to adulthood, although these effects are not as consistent as observed in F0 following direct exposure