In utero marijuana exposure associated with abnormal amygdala dopamine D2 gene expression in the human fetus

Background: (Cannabis sativa) is the illicit drug most used by pregnant women, and behavioral and cognitive impairments have been documented in cannabis-exposed offspring. Despite the extensive use of marijuana, very limited information exists as to the consequences of prenatal cannabis exposure on the developing human brain. Methods: We optimized an in situ hybridization histochemistry technique to visualize mRNA expression in midgestation (weeks 18-22) human fetal specimens from mothers with and without documented evidence of cannabis use during pregnancy. The cannabinoid receptor type I (CB1) and major dopamine receptor subtypes, D-1 and D-2, were examined in the striatum and mesocorticolimbic structures (amygdala and hippocampus). Results: Adjusting for various covariates, we found a specific reduction, particularly in male fetuses, of the D-2 mRNA expression levels in the amygdala basal nucleus in association with maternal marijuana use. The reduction was positively correlated with the amount of maternal marijuana intake during pregnancy. No significant cannabis-related alterations were detected in the hippocampus or caudal striatum for the D-2 ,D-1, and CB1 mRNA levels, although alcohol showed significant contribution to striatal D-1/D-2 expression. Conclusions: These human fetal findings suggest that in utero cannabis exposure may impair distinct mesocorticolimbic neural systems that regulate emotional behavior.