Prenatal THC exposure altered dopamine receptor genes and brain cell excitability in adolescent male rats

Prenatal cannabis exposure increased mRNA levels of dopamine D1 and D2 receptors in the prefrontal cortex, with a particularly strong effect on D2 in males. Male rats showed reduced Drd2 DNA methylation (potentially explaining increased expression), changes in selective miRNAs regulating both receptors, altered excitability of prefrontal pyramidal neurons, and disrupted Netrin-1/DCC guidance cue system. Endocannabinoid system gene expression remained stable.

An animal model of prenatal cannabis exposure was used, with offspring studied during adolescence. Researchers analyzed gene expression and DNA methylation of dopamine and endocannabinoid system genes in the prefrontal cortex, measured miRNA regulators, performed electrophysiological recordings of pyramidal neurons, and assessed the Netrin-1/DCC guidance cue system.

The prefrontal cortex is critical for decision-making, impulse control, and emotional regulation, and it undergoes major development during adolescence. Finding that prenatal THC exposure reprograms dopamine signaling in this region through epigenetic mechanisms provides a biological pathway that could explain behavioral and psychiatric risks associated with prenatal cannabis exposure.

The sex-specific nature of these findings is consistent with human epidemiological data showing that males may be more vulnerable to some neurodevelopmental effects of prenatal cannabis exposure. The epigenetic mechanism (DNA methylation changes) suggests these are not transient effects but persistent reprogramming of gene regulation that manifests during the critical adolescent period.

Animal model using controlled THC exposure that may not reflect human prenatal exposure patterns. Only adolescent timepoint was assessed; effects may differ at other ages. The specific THC dose and timing were not detailed in the abstract. Translation from rodent prefrontal cortex to human is imperfect.