Advancing a Pre-Clinical Model of Full-Term Prenatal Exposure to Vaporized Δ9-Tetrahydrocannabinol.

INTRODUCTION

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.

MATERIALS AND

METHODS

Pregnant female Sprague-Dawley rats were exposed to THC (200 mg/mL, n = 13) or vehicle (100% propylene glycol, n = 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 (n = 4 dams, 24 pups) or PD 10 (n = 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).

RESULTS

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.

DISCUSSION: 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.