Sex‐specific alterations in cognitive control following moderate prenatal alcohol exposure and transient systemic hypoxia ischemia in the rat

• Published in: Alcohol, clinical & experimental research clinical & experimental research, 2024-04, Vol.48 (4), p.640-652
• Main Authors: Dunn, Brooke R., Olguin, Sarah L., Davies, Suzy, Pavlik, Nathaniel G., Brigman, Jonathan L., Hamilton, Derek, Savage, Daniel D., Maxwell, Jessie R.
• Format: Article
• Language: English
• Subjects: cognitive testing; moderate prenatal alcohol exposure; touchscreen operant platform paradigm; transient systemic hypoxia ischemia
• ISSN: 2993-7175; 2993-7175
• DOI: 10.1111/acer.15276

Background Prenatal alcohol exposure (PAE) continues to be a worldwide problem. Affected offspring display impaired neurodevelopment, including difficulties with executive control. Although PAE has also been associated with decreased blood flow to fetuses, the relationship between PAE and altered blood flow is not well understood. Methods We used preclinical models of PAE, transient systemic hypoxia ischemia (TSHI), and PAE + TSHI combined to assess the effects on neurodevelopmental outcomes using translationally relevant touchscreen operant platform testing. Twenty‐eight Long–Evans (Blue Spruce, Strain HsdBlu:LE) dams were randomly assigned to one of four experimental groups: Saccharin Control (Sham), 5% Ethanol (PAE), TSHI, or 5% Ethanol and TSHI (PAE + TSHI). Dams consumed either saccharin or 5% ethanol during gestation. TSHI was induced on Embryonic Day 19 (E19) during an open laparotomy where the uterine arteries were transiently occluded for 1 h. Pups were born normally and, after weaning, were separated by sex. A total of 80 offspring, 40 males and 40 females, were tested on the 5‐Choice Continuous Performance paradigm (5C‐CPT). Results Female offspring were significantly impacted by TSHI, but not PAE, with an increase in false alarms and a decrease in hit rates, omissions, accuracy, and correct choice latencies. In contrast, male offspring were mildly affected by PAE, but not TSHI, showing decreases in premature responses and increases in accuracy. No significant interactions between PAE and TSHI were detected on any measure. Conclusion Transient systemic hypoxia ischemia impaired performance on the 5C‐CPT in females, leading to a bias toward stimulus responsivity regardless of stimulus type. In contrast, TSHI did not affect male offspring, and only slight effects of PAE were seen. Together, these data suggest that TSHI in females may cause alterations in cortical structures that override alterations caused by moderate PAE. We explored the interaction of prenatal alcohol exposure (PAE) and transient systemic hypoxia ischemia (TSHI) in a rat model to understand how these factors alternated cognitive control using a translational touchscreen behavioral paradigm. In females, TSHI led to an increase in touch responsivity regardless of PAE status. In males, PAE increased accuracy and decreased premature responses regardless of TSHI status. Our data contributes to the growing knowledge of the interaction of PAE and blood flow on neurodevelopmental outcom