Perinatal Tetrahydrocannabinol Compromises Maternal Care and Increases Litter Attrition in the Long–Evans Rat

TL;DR

Perinatal THC exposure in rats impairs maternal care and increases pup mortality, suggesting potential risks for offspring development.

Contribution

This study identifies maternal care as a previously overlooked index of THC toxicity in rats.

Findings

THC exposure impaired maternal pup retrieval and increased pup mortality in rats.

Benchmark doses for reduced pup retrieval and increased mortality were 0.383 and 0.794 mg/kg THC, respectively.

THC levels in dams were comparable to those in breastfeeding chronic users.

Abstract

The marijuana legalization trend in the U.S. will likely lead to increased use by younger adults during gestation and postpartum. The current study examined the hypothesis that delta-9-tetrahydrocannabinol (THC) would disrupt voluntary maternal care behaviors and negatively impact offspring development. Rat dams were gavaged with 0, 2, 5, or 10 mg/kg THC from the 1st day of gestation through the 21st postnatal day. Somatic growth and developmental milestones were measured in the offspring, and maternal pup retrieval tests were conducted on postnatal days 1, 3, and 5. THC did not affect body growth but produced transient delays in the righting reflex and eye opening in offspring. However, there was significant pup mortality due to impaired maternal care. Dams in all THC groups took significantly longer to retrieve their pups to the nest and often failed to retrieve any pups. Serum levels of THC and metabolites measured at this time were comparable to those in breastfeeding women who are chronic users. Benchmark doses associated with a 10% reduction of pup retrieval or increased pup mortality were 0.383 (BMDL 0.228) and 0.794 (BMDL 0.442) mg/kg THC, respectively. The current findings indicate that maternal care is an important and heretofore overlooked index of THC behavioral toxicity and should be included in future assessments of THC’s health risks.

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