Prenatal THC exposure disrupted spatial memory in adolescent male rats more than females

Prenatal THC exposure caused sex-specific disruption in spatial memory retrieval and flexibility. Males showed decreased density of CCK-positive basket cells (inhibitory interneurons) and increased neuroplasticity markers. Females showed delayed memory retrieval but preserved flexibility, increased CCK+BC density, and mostly preserved neuroplasticity markers.

Sprague Dawley dams received THC (2 mg/kg) or vehicle from gestational day 5-20. Adolescent offspring were tested in the Barnes Maze for spatial memory. Hippocampal tissue was analyzed for CCK+BC density, neuroplasticity gene expression, and neuroligin isoform expression.

This study provides biological mechanisms for why prenatal cannabis exposure might affect brain development differently in males and females, specifically through disruption of the excitatory/inhibitory balance in the hippocampus.

With prenatal cannabis exposure increasing alongside legalization, understanding sex-specific developmental effects is critical. The finding that males and females show opposite changes in inhibitory interneuron density suggests fundamentally different biological responses to prenatal THC.

Animal model using a single THC dose that may not reflect typical human prenatal exposure patterns. Rats were exposed throughout most of gestation, while human exposure patterns vary. Adolescent testing only, so long-term adult outcomes are unknown.