Vape flavorants dull sensory perception and cause hyperactivity in developing zebrafish embryos

E-cigarette use (vaping) during pregnancy has been increasing, and the potential exists for the developing brain in utero to be exposed to chemical constituents in the vape. Vapes come in over 7,000 unique flavors with and without nicotine, and while nicotine is a known neurotoxicant, the effects of vape flavoring alone, in the absence of nicotine, on brain function are not well understood. Here we performed a screen of vape aerosol extracts (VAEs) to determine the potential for prenatal neurotoxicity using the zebrafish embryo photomotor response (PMR) – a translational biosensor of neurobehavioral effects. We screened three commonly used aerosolized vape liquids (flavored and flavorless) either with or without nicotine. No neurobehavioral effects were detected in flavorless, nicotine-free VAEs, while the addition of nicotine to this VAE dulled sensory perception. Flavored nicotine-free VAEs also dulled sensory perception and caused hyperactivity in zebrafish embryos. The combination of flavor and nicotine produced largely additive effects. Flavored VAEs without nicotine had similar neuroactive potency as nicotine. Similar effects were also seen in embryos exposed to the pure flavoring compound, cinnamaldehyde. Together, using zebrafish PMR as a high throughput translational behavioral model for prenatal exposure, our results demonstrate that e-cigarette flavorants that we screened elicit neurobehavioral effects worthy of further investigation for long-term neurotoxic potential, and also have the potential to modulate nicotine impact on the developing brain.

Methods
The data were collected as described in the methods section of main article.