High-Salt Exposure During Perinatal Development Enhances Stress Sensitivity

Excess consumption of dietary sodium during pregnancy has been shown to impair offspring cardiovascular function and enhance salt preference in adulthood, but little is known regarding the long-term impact of this nutritional surplus on offspring brain morphology and behavior. Using a combination of cellular and behavioral approaches, we examined the impact of maternal salt intake during the perinatal period on structural plasticity in the prefrontal cortex (PFC) and nucleus accumbens (NAc) in weanling and adult offspring as well as reward- and stress-driven behaviors in adult offspring. We found that weanling rats born to 4% NaCl-fed dams exhibited an increase and decrease in thin spine density in the infralimbic PFC (IL-PFC) and prelimbic PFC (PL-PFC), respectively, as well as an increase in mushroom spine density in the NAc shell, compared to 1% NaCl-fed controls. Structural changes in the IL-PFC and NAc shell persisted into adulthood, the latter of which is a phenotype that has been observed in rats exposed to early life stress. There was no effect of maternal salt intake on reward-driven behaviors, including sucrose preference, conditioned place preference (CPP) for cocaine, and forced swim stress (FSS)-induced reinstatement of cocaine-induced CPP. However, rats born to high-salt fed dams spent less time swimming in the FSS and displayed heightened plasma CORT levels in response to the FSS compared to controls, suggesting that early salt exposure increases stress sensitivity. Overall, our results suggest that perinatal salt exposure evokes lasting impacts on offspring physiology and behavior.