Prenatal Coca Paste Exposure Impairs Hippocampal Neuronal Development and Recognition Memory in Offspring.

Abstract

Illicit psychostimulant use during pregnancy represents a major public health issue due to its detrimental effects on offspring neurodevelopment. Prenatal exposure to smokable cocaine derivatives such as crack cocaine and coca paste (CP) is particularly concerning, as it has been associated with an increased risk of impairments in learning, memory, and social behavior from birth through early childhood. CP's low cost, wide availability, high toxicity, and strong addictive potential heighten its danger. While CP use during pregnancy is well documented, its specific neurodevelopmental consequences remain poorly understood compared to those of crack. Here, we used a rat model to examine the effects of chronic prenatal exposure to a street-grade CP sample obtained from police seizures on hippocampal neuronal morphogenesis, synaptogenesis, and function, as well as hippocampus-dependent recognition memory. Primary hippocampal neurons from neonates prenatally exposed to CP once daily from gestational day (GD) 8 until GD21 showed reduced neuronal survival, impaired neurite outgrowth, and decreased dendritic complexity, together with reduced synaptic vGlut1 abundance. These structural alterations were accompanied by significant deficits in recognition memory in the novel object recognition task in juvenile offspring. Our findings suggest that prenatal CP exposure disrupts hippocampal development and function, leading to cognitive deficits. This study supports the severe neurodevelopmental risks associated with prenatal CP exposure and underscores the importance of preventive strategies addressing drug use during pregnancy.