Prenatal THC exposure produces a hyperdopaminergic phenotype rescued by pregnenolone
R. Frau, Vivien Miczán, F. Traccis, Sonia Aroni, C. Pongor, P. Saba, V. Serra, Claudia Sagheddu, Silvia Fanni, M. Congiu, P. Devoto, Joseph Cheer, István Katona, Miriam Melis
Nature Neuroscience September 11, 2019 DOI: 10.1038/s41593-019-0512-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Rat offspring of THC-exposed dams |
| Interventions | Δ9-tetrahydrocannabinol (THC) Pregnenolone |
| Topics | Cannabis |
| Key points | Prenatal cannabis exposure in male rat offspring leads to hyperdopaminergic state and behavioral sensitivity, which can be rescued by the neurosteroid pregnenolone. |
Abstract
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 Δ9-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. In offspring exposed to THC in utero, molecular, synaptic and circuit reorganizations lead to a hyperdopaminergic phenotype and behavioral susceptibility. The neurosteroid pregnenolone restores both dopamine function and abnormal behavior.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 22
- Long-term hippocampal interneuronopathy drives sex-dimorphic spatial memory impairment induced by prenatal THC exposure Neuropsychopharmacology January 26, 2020
- Vaporized Δ9-tetrahydrocannabinol exposure in utero has negative effects on attention in a dose- and sex-dependent manner. Pharmacology, Biochemistry, and Behavior September 1, 2024
- Psychotomimetic compensation versus sensitization. Pharmacology Research & Perspectives August 1, 2024
- Adult Rat Offspring Exposed to THC during Gestation Exhibit Distinct Biomolecular Changes Identified by X-ray Fluorescence Imaging and Fourier Transform Infrared Spectroscopy in Cortico-Limbic Circuits. ACS Chemical Neuroscience February 18, 2026
- Prenatal cannabinoid exposure alters excitation-inhibition balance through glutamate and GABA receptor-mediated signaling. Journal of Biological Chemistry July 2026
and 17 more in the library
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