EXPOSURE TO NICOTINE AND CANNABIS DURING PREGNANCY RESULTS IN IMPAIRMENTS IN SOCIAL BEHAVIOR

The frequent co-use of nicotine and cannabis, coupled with rising e-cigarette use and cannabis legalization, makes it increasingly important to understand their combined effects. Vape exposure during pregnancy poses a significant global issue. Both Nicotine and Δ9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, cross the placental barrier and can alter fetal brain circuits underlying social and cognitive development, potentially influencing vulnerability to neuropsychiatric disorders.
This study investigates the sex-specific effects of prenatal Nicotine and/or THC vapor exposure on social behavior, communicative signaling, and voluntary drug intake in a preclinical model. Adult female Wistar rats were exposed daily to Nicotine (5mg/ml) and/or THC vapor (25mg/ml) or vehicle beginning five days before mating and continuing through gestational day (GD) 20. Offspring were drug-naïve postnatally, and social interaction was assessed in adolescence, postnatal day (PND) 24, and adulthood (PND 54) using a three-chambered apparatus. Ultrasonic vocalizations (USVs) were recorded at PND 5 and PND 21 and analyzed with DeepSqueak. At PND 55, offspring were enrolled in the vape self-administration preference (VSAP) paradigm, enabling voluntary lever-pressing for nicotine vapor, THC vapor, or both.
Our data suggest that prenatal THC exposure reduces social exploration and alters distress-related USVs, particularly in female pups. Female offspring self-administered more drugs compared with males, and both sexes showed a strong preference for THC. These findings underscore the complex, sex-specific neurobehavioral effects of prenatal cannabis exposure and highlight the importance of considering biological sex when evaluating developmental risks and the neural circuits underlying social behavior.