Innovative Methods for Prenatal Cannabis Exposure: Vapor Inhalation Chamber and Metabolite Quantification in Prairie Voles and Rats

The increasing prevalence of cannabis use, including among pregnant women, highlights the critical need for a deeper understanding of prenatal cannabis exposure. This study aimed to develop a standardized cross-species inhalation exposure protocol to administer the principal psychoactive component of cannabis, {Delta}9-tetrahydrocannabinol (THC), to prairie voles (Microtus ochrogaster) and laboratory rats (Rattus norvegicus), and to investigate the distribution of THC in maternal and fetal tissues following prenatal exposure. Using an established e-cigarette system for delivering vaporized THC, we administered THC to pregnant prairie voles and rats. THC concentrations were measured in maternal plasma and fetal brain tissue using LC-MS/MS (Liquid Chromatography coupled with Tandem Mass Spectrometry). In both species, THC levels were compared across groups to evaluate the impact of fetal position on THC uptake. We found that THC readily crossed the placental barrier in both species, resulting in significantly higher concentrations of THC in the fetal brain within the THC-exposed groups compared to the vehicle controls. Interspecies comparison revealed higher THC concentrations in rat fetal brain tissue compared to prairie voles. No significant effects of fetal position on THC levels were found for either species. The findings confirm placental transfer of THC and reveal species-specific patterns of THC distribution. Additional studies were then carried out in voles to compare plasma and brain THC levels in maternal and virgin adult prairie voles. Maternal brain THC concentrations were significantly higher than fetal brain concentrations in prairie voles. Strong positive correlations were observed between plasma and brain THC concentrations in both maternal and virgin adult prairie voles. This study establishes a translational model for investigating prenatal cannabis exposure using an aerosolized administration method in voles compared to established methods in rats. The standardized protocol and results provide a foundation for future research into the developmental consequences of prenatal cannabis exposure and offer crucial insights for informing public health policies and clinical practices in response to the global increase in cannabis use.