Menu Close

Perinatal Cannabidiol Exposure Decreases Survival in Mice, and Impacts Anxiety-like and Obsessive Compulsive-like Behavior and Object Memory in a Sexually Dimorphic Manner When Raised to Adult

Alexis Cox
Florida State University

Co-authors: Tyla Dolezel1, Claudia Silver1, Aidan Carley1, Alejandro Navarez1, Destinee Gatlin1, Ezabelle Franck1, Ryan Ochoa1, Debra Ann Fadool1
1Florida State University

Objective: Anxiety, attention, and memory were examined in adult mice following gestational exposure to cannabidiol (CBD), the non-psychoactive ingredient of cannabis. Administration of oral CBD to the pregnant dam was hypothesized to dampen offspring anxiety behaviors when raised to adult.

Methods: Sexually naïve dams were trained to eat 100 mg of strawberry jam from a dish. Following acclimation and two weeks prior to mating, 100 mg/kg CBD or ethanol vehicle was mixed in the jam and administered daily to provide drug treatment throughout gestation and lactation. Once pups were born, some litters were cross-fostered to vehicle treated dams to separate any effects of CBD-induced changes in maternal behavior. At 3 months of age, offspring were behaviorally phenotyped using the buried marble, light-dark box (LDB), elevated plus maze (EPM), object memory recognition, and object attention tasks.

Results: Pups born to CBD-treated mothers had a reduced survival – 62.2% of pups died before being weaned, whereas only 9.5% of non-drug treated pups died. We did not observe changes in litter size, maternal body weight or pup birth weight (postnatal day 0, P0), however, pups born to CBD-treated mothers weighed significantly greater by P10 and P21. In utero exposure caused mice of both sexes to bury more marbles, and females, not males, lost this behavior if they were cross-fostered to control 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 or the 1-hour object recognition test but it decreased performance of female mice in the 24-hour object recognition test.

Conclusion: In conclusion, our data showed that gestational CBD decreases survival and may produce long-lasting anxiolytic effects for adult female mice. Gestational CBD increases obsessive compulsive-like behavior in adults, which can be reversed in females by early maternal behaviors. Gestational CBD does not alter ADHD-like behavior but decreases long-term memory in female mice as adults.

Leave a Reply