Prenatal alcohol use linked to increased offspring addiction risk

During a discussion with Contemporary OB/GYN, Rajesh Miranda, PhD, and Jun Wang, PhD, professors at Texas A&M University College of Medicine, outlined emerging data on the neurodevelopmental consequences of prenatal alcohol exposure (PAE) and its potential mechanistic links to later-life addiction vulnerability.

Miranda began by emphasizing that PAE has been well documented for nearly 4 decades to produce consistent structural and functional alterations in the developing fetus. In both human populations and animal models, these effects typically manifest as fetal and childhood growth restriction, low birth weight, and an array of neurobehavioral impairments.

Common deficits include attention and hyperactivity disorders, speech and language delays, hearing impairment, memory problems, and other cognitive challenges. These early deficits often compound over time, interacting with school environments and social systems to generate more severe functional impairments and heightened risk for adolescent or early adult substance use disorders.

Wang expanded on these observations by presenting new mechanistic findings derived from collaborative work with Miranda's group. His research focuses on cholinergic interneurons—specialized neurons that release acetylcholine and are essential for cognitive flexibility and adaptive behavioral responses.

These neurons are also implicated in neurodegenerative diseases such as Alzheimer’s disease. The investigators used established rodent models in which animals are exposed to alcohol prenatally and perinatally, allowing for controlled evaluation of neurobiological and behavioral outcomes independent of confounding environmental stressors.

According to Wang, offspring with PAE demonstrated a significant reduction in the number of cholinergic interneurons in a region corresponding to the human medial striatum, as well as notable disruptions in their electrophysiologic function. In typical conditions, these neurons fire at 2 to 5 hertz and exhibit characteristic burst–pause patterns that regulate acetylcholine release—patterns critical for learning, strategy shifting, and environmental adaptability.

In PAE-exposed offspring, both the burst frequency and the subsequent pause dynamics were altered. The shortened pause period in particular limited acetylcholine availability, thereby diminishing opportunities for new learning and impairing cognitive flexibility.

Behaviorally, these animals could acquire new tasks but struggled to revise learned strategies, a hallmark of impaired behavioral flexibility. They also displayed compulsive tendencies, including patterns resembling excessive or compulsive drinking. Using advanced sensor technologies, the researchers confirmed reduced acetylcholine release in real time during behavioral testing.

Miranda noted that these controlled findings are especially valuable because, in humans, PAE-associated addiction risk is difficult to disentangle from early-life trauma, instability, and environmental adversity. The animal data, however, isolate prenatal exposure as a direct causal factor, providing rare mechanistic clarity and advancing understanding of Fetal Alcohol Spectrum Disorder-related addiction vulnerability.

This video is part 1 of a 2-part series. Check back tomorrow for part 2.

No relevant disclosures.

Reference

Purvines W, Gangal H, Xie X, et al. Perinatal and prenatal alcohol exposure impairs striatal cholinergic function and cognitive flexibility in adult offspring. Neuropharmacology. 2025;279:110627. doi:10.1016/j.neuropharm.2025.110627