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Health and Behavioral Consequences of Perinatal Cannabidiol Exposure in Mice Raised to Adult

Martina Compagno
Florida State University

Co-Authors: Caroline Bishop1, Aidan Carley1, Joshua Cazorla1, Jenna Claydon1, Alexis Cox1, Tyla Dolezel1, Ezabelle Franck1, Camilla Ann May1, Alejandro Navarez1, Claudia Rose Silver1, Olivia Turner1, Kari B. Basso2, Debra Ann Fadool1
1Florida State University 2University of Florida

Anxiety- and attention-like behaviors, and memory were examined in adult mice following gestational and lactational exposure to cannabidiol (CBD), the non-psychoactive ingredient of cannabis. Primiparous dams were trained to orally consume 100 mg/kg CBD or ethanol vehicle mixed in strawberry jam. Using GC-MS, we were able to detect 40 ng/ul CBD in maternal plasma within 1 h following oral consumption. There was no significant difference in the rate of retrieval of displaced pups back to the nest by CBD-treated dams, indicating lack of drug-induced changes in maternal behavior (2-W ANOVA, p>0.05). Fetal exposure to CBD significantly decreased survival of the pups – 37% of CBD-treated pups died before weaning age (23 days) whereas only 14% of jam-treated pups died prior to weaning. Cross-fostering of CBD-treated pups to a drug-free dam did not improve survival rates (38% died prior to weaning). We did not observe changes in litter size, maternal body weight or pup birth weight (postnatal day 1, P1) between CBD vs. jam-treated animals, however, by postnatal day 10 and 21 (P10, P21), CBD-exposed mice weighed significantly more. CBD-exposed female mice cleared glucose slower than those of jam-treated mice, indicating predisposition for metabolic disorder as an adult (2w RM ANOVA, treatment x time interaction, p=0.0078). At 3 months of age, adult offspring were behaviorally phenotyped. In utero exposure caused mice of both sexes to bury more marbles as adults (1-W ANOVA, p≤0.05), and females, not males, lost this behavior if they were cross-fostered to control, drug-free dams. In utero exposure decreased time spent in the light compartment of an LDB apparatus when females were raised to adults, but had no effect on male mice. In utero exposure did not affect performance in an object attention task (ADHD-like behavior) or the 1-hour object recognition test (short-term memory) but it decreased performance of female mice in the 24-hour object recognition test (long-term memory; p=0.01279). Perinatal CBD therefore increases obsessive compulsive behavior in both sexes, while it decreases anxiety-like behavior and long-term memory in female mice raised to adults.

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