Prenatal Exposure to Vaporized High‐Potency Cannabis Affects Hippocampal Synaptic Remodeling and Efficacy, Axonal Excitability, and Memory in Offspring

Cannabis use during pregnancy has recently become an important concern due to its increasing trend and association with neurodevelopmental alterations of exposed children. Although inhalation is the primary route of cannabis consumption in humans, few studies replicated this route in preclinical models of prenatal exposure. This study aimed to analyze the effects of chronic prenatal exposure to vaporized cannabis (PEVC) on hippocampal neurodevelopment, functionality, and learning and memory processes. Using a commercially available high-potency cannabis strain (THC 14.7%), pregnant rats were exposed to cannabis vapor from gestational day 8 to 21. A combination of primary hippocampal cultures, electrophysiological studies in slices, and behavioral tests was employed to assess the impact of PEVC. We found that PEVC induced presynaptic remodeling of hippocampal neurons in offspring under both basal and activity-dependent conditions by increasing synaptic vGlut1 abundance and the total recycling pool of synaptic vesicles. Chronic PEVC also induced a downregulation of CB1R at glutamatergic and GABAergic synapses. Additionally, an increase in axonal recruitment and synaptic efficacy was observed at hippocampal CA1 synapses of juvenile offspring. Moreover, long-lasting cognitive impairments were identified during adolescence, including deficits in spatial memory in male and female offspring. In summary, these findings demonstrate that exposure to high-potency cannabis vapor during pregnancy leads to significant changes in synaptic remodeling and efficacy, axonal recruitment, and long-term cognitive consequences in offspring.