Red Flags for Fetal Brain Development
How does THC exposure during pregnancy affect dopamine signaling in the fetal brain?
Jonathan James | | Quick Read
A new study adds weight to existing evidence that using cannabis during pregnancy may impair fetal brain development. Male rats whose mothers were exposed to THC during pregnancy showed extensive changes in dopamine function and were more susceptible to the effects of THC in pre-adolescence (1). Administering pregnenolone, a drug that inhibits downstream CB1 receptor activation, to the offspring appeared to reverse these changes. We spoke with one of the researchers involved in the study, Miriam Melis, to learn more.
What was the rationale behind the project?
We know that vulnerability to neuropsychiatric disorders depends upon the interaction of biological and environmental factors – particularly during infant brain development. One of the key environmental risk factors is early exposure to drugs of abuse – and cannabis is the most common drug used by pregnant women. Human studies examining the long-term consequences of exposure in offspring have demonstrated behavioral and cognitive abnormalities, yet all such studies have focused on the effects on those brain regions containing dopamine-releasing neurons. Until our study, nobody had looked at the regions where dopamine-containing neurons reside (such as the ventral tegmental area) despite their pivotal role in many disorders.
What’s the link between dysfunctional dopamine signaling and neuropsychiatric impairment?
Aberrant dopamine signaling is implicated in a diverse range of neuropsychiatric disorders, including schizophrenia. We’ve shown that prenatal cannabis exposure deranges the normal development of these systems; however, we still don’t know if it alters the intrinsic excitability of dopamine neurons or causes changes in the homeostatic mechanisms that maintain proper dopamine system function.
What are the next steps in your research?
We’d like to understand how pregnenolone works to reprogram the dopamine system. In parallel, we want to understand why male – but not female – offspring were affected. Part of that work will involve looking at other drugs of abuse, to determine whether there are common pathways by which these substances act on the developing brain.
- R Frau et al., “Prenatal THC exposure produces a hyperdopaminergic phenotype rescued by pregnenolone”, Nat Neurosci, 12, 1975 (2019). DOI: 10.1038/s41593-019-0512-2