Summary:
This study was a 20-year prospective longitudinal experimental study in rhesus monkeys that examined whether prenatal exposure to moderate alcohol and mild maternal stress alters the offspring dopamine system and impacts alcohol-drinking behaviour later in life. The research question is difficult to answer in humans because intentionally exposing pregnant people to alcohol or stress for experimental purposes is unethical and controlled randomisation of prenatal alcohol exposure risks fetal harm. Pregnant monkeys were randomly assigned to one of four conditions: moderate alcohol exposure, mild stress exposure, both exposures, or neither. Their offspring were then followed into adulthood and imaging was used to measure dopamine availability in brain regions involved in reward and executive control. Measurements were taken at baseline and again after the offspring completed a period of alcohol consumption. The animals were then given unrestricted access to alcohol to assess voluntary intake. This study found that prenatal stress exposure was associated with increased dopamine availability, indicating altered dopamine regulation. Changes were also seen in the brain region responsible for decision-making and impulse control. Prenatal alcohol exposure alone was associated with a faster rate of fixed-dose alcohol consumption in adulthood. Overall, this study demonstrates that the primate dopamine system is highly sensitive to prenatal environmental exposures. The findings support the hypothesis that vulnerability to alcohol misuse may originate during fetal development. These results align with extensive human evidence showing that alcohol readily crosses the placenta and can disrupt fetal brain development and that maternal stress can further influence fetal brain development through inflammatory signalling. Although findings from animal models must be translated cautiously, the controlled experimental design in this primate study provides important insight that cannot be ethically obtained in humans and strengthens concerns that even moderate prenatal alcohol exposure may contribute to later vulnerability to substance use.
Abstract:
Given the prevalence of alcohol use and stress during pregnancy, we examined the effects in offspring of prenatal alcohol and stress on the dopamine system and drinking behavior in a primate model. In a 20-year prospective longitudinal experiment, we studied alcohol-naive adult rhesus monkeys of both sexes bred from mothers randomly assigned during pregnancy to consume moderate alcohol, be exposed to mild stress, both, or neither. Positron emission tomography (PET) was used to measure dopamine D2-type receptor (D2) and transporter (DAT) availability in substantia nigra/ventral tegmental area (SN/VTA), striatum, and prefrontal cortex (PFC), at baseline and after chronic fixed-dose drinking in offspring. After the follow-up PET scans, monkeys were given ad libitum access to alcohol. Findings were: (1) prenatal stress increased DAT in SN/VTA and striatum, while an interaction of prenatal stress and alcohol altered D2 in PFC; (2) prenatal alcohol alone increased the fixed-dose drinking rate; (3) in the three brain regions, low baseline D2 predicted faster fixed-dose drinking rate, and changes in DATA from baseline to follow-up predicted consumption in subsequent ad libitum drinking; and (4) no significant alteration of D2 or DAT due to drinking was observed. This experiment highlights the sensitivity of the primate dopamine system to prenatal perturbations, dopamine’s role in drinking, and an individual neuroadaptive response to chronic alcohol consumption. The results suggest that alcohol abuse may originate, in part, from prenatal alcohol exposure. Moreover, reports in AUD of lower D2 might reflect preexisting dopamine receptor status rather than resulting entirely from alcohol consumption.
Article Publication Date: 11/02/2026
DOI: 10.1523/JNEUROSCI.0717-25.2026
