Abstract
<h4>Introduction</h4>Use of cannabinoid vape products during pregnancy is a major public health concern. Δ9-tetrahydrocannabinol (THC), the main psychoactive constituent in cannabis, is rapidly absorbed after inhalation and transferred to the fetal brain. We developed a novel model of prenatal cannabinoid exposure (PCE) comprising THC vapor exposure across the human-equivalent full-term prenatal period in rats. This study examined gestational/parturitional outcomes and the distribution and metabolism of THC in maternal and filial blood and brains using this model.<h4>Materials and methods</h4>Pregnant female Sprague-Dawley rats were exposed to THC (200 mg/mL, <i>n</i> = 13) or vehicle (100% propylene glycol, <i>n</i> = 8) vapor daily during gestation until postnatal day (PD) 10 (i.e., human-equivalent full-term). Pups were exposed directly in the postnatal period. Gestational/parturitional assessments included dam food intake, dam and pup body weights, total gestation days, litter size, and sex ratio. Subsets of THC-exposed dams and pups were sampled immediately postvapor on gestational day (GD) 20 (<i>n</i> = 4 dams, 24 pups) or PD 10 (<i>n</i> = 2 dams, 33 pups) to quantify THC and its metabolites (11-hydroxy-Δ9-tetrahydrocannabinol [11-OH-THC], and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol [THCCOOH]) concentrations in the brain (dams and pups) and plasma (dams).<h4>Results</h4>THC decreased dam food intake and total gestation days compared to controls. THC concentrations in dam plasma and brain were 14.8 ± 47.8 ng/mL and 80.5 ± 38.6 ng/g on GD 20 and 68.9 ± 25.0 ng/mL and 125.0 ± 4.2 ng/g on PD 10. Birth weights were not different between THC-exposed offspring and controls, but postnatal weights were decreased. On GD 20, fetal brain THC, 11-OH-THC, and THCCOOH concentrations were 12 ± 5%, 118 ± 7%, and 75 ± 34% of maternal plasma. On PD 10, pup brain THC and 11-OH-THC concentrations were 29.6 ± 8.5 and 9.8 ± 2.1 ng/g. THCCOOH was not detected in PD 10 pup brain.<h4>Discussion</h4>THC readily transferred from dams to pup brains during gestation in our full-term vapor exposure model. High THC and 11-OH-THC concentrations were detected in pup brains at both timepoints. This novel model is a valuable tool to investigate long-term effects of full-term PCE on offspring brain development and behavior.
Authors
Jenkins BW, Moore CF, Tiwari P, Lichtman AH, Poklis JL, Jantzie LL, Weerts EM