Prenatal THC exposure produces a hyperdopaminergic phenotype rescued by pregnenolone
Prenatal THC exposure produces a hyperdopaminergic phenotype rescued by pregnenolone
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DOI：
10.1038/s41593-019-0512-2
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发表时间：
2019-12-01
影响因子：
25
通讯作者：
Melis, Miriam
中科院分区：
文献类型：
--
作者：
Frau, Roberto;Miczan, Vivien;Melis, Miriam
The increased legal availability of cannabis has led to a common misconception that it is a safe natural remedy for, among others, pregnancy-related ailments such as morning sickness. Emerging clinical evidence, however, indicates that prenatal cannabis exposure (PCE) predisposes offspring to various neuropsychiatric disorders linked to aberrant dopaminergic function. Yet, our knowledge of how cannabis exposure affects the maturation of this neuromodulatory system remains limited. Here, we show that male, but not female, offspring of Delta(9)-tetrahydrocannabinol (THC)-exposed dams, a rat PCE model, exhibit extensive molecular and synaptic changes in dopaminergic neurons of the ventral tegmental area, including altered excitatory-to-inhibitory balance and switched polarity of long-term synaptic plasticity. The resulting hyperdopaminergic state leads to increased behavioral sensitivity to acute THC exposure during pre-adolescence. The neurosteroid pregnenolone, a US Food and Drug Administration (FDA) approved drug, rescues synaptic defects and normalizes dopaminergic activity and behavior in PCE offspring, thus suggesting a therapeutic approach for offspring exposed to cannabis during pregnancy.
