Prenatal THC exposure produces a hyperdopaminergic phenotype rescued by pregnenolone
Nature Neuroscience September 11, 2019 R. Frau, Vivien Miczán, F. Traccis et al.
Prenatal cannabis exposure (PCE) in a rat model causes extensive molecular and synaptic changes in dopamine neurons of the ventral tegmental area, specifically in male offspring. These changes include altered excitatory-to-inhibitory balance and switched polarity of long-term synaptic plasticity, leading to a hyperdopaminergic state and increased behavioral sensitivity to acute THC exposure during pre-adolescence. The neurosteroid pregnenolone, an FDA-approved drug, rescues synaptic defects and normalizes dopaminergic activity and behavior in PCE offspring, suggesting a potential therapeutic approach for offspring exposed to cannabis during pregnancy.