The Combined Effects of Perinatal Ethanol and Early-Life Stress on Cognition and Risk-Taking Behavior through Oxidative Stress in Rats

Both prenatal ethanol and early-life stress have been shown to induce reduced risk-taking and explorative behavior as well as cognitive dysfunction in the offspring. In this study, we examined the effect of combined exposure to ethanol and early stress on maternal care, exploratory behavior, memory performances, and oxidative stress in male offspring. Pregnant rats were exposed to ethanol (4 g/kg) from gestational day (GD) 6-to postnatal day (PND) 14 and limited nesting material (LNS) from PND0-PND14 individually or in combination. Maternal behavior was evaluated during diurnal cycle. The level of corticosterone hormone and markers of oxidative stress were evaluated in the pups. Risk-taking and explorative behavior were assessed with the elevated-plus maze (EPM) test and cognitive behavior with the Morris water maze (MWM), novel object recognition (NORT), and object location memory (OLM) tests. In the mothers, perinatal alcohol or LNS either alone or in combination decreased maternal behavior. In the offspring, the combination of the two factors significantly increased the pup's plasma corticosterone concentration in comparison with ethanol and LNS alone. Reduced risk-taking behavior was observed in the ethanol, LNS and ethanol + LNS groups compared with the control group, and this was amplified in the co-exposure of ethanol and LNS groups. The MWM, NORT, and OLM tests revealed spatial and recognition memory impairment in the ethanol and LNS groups. This impairment was more profound in the co-exposure of ethanol and LNS. Also, we observed a significant decrease in superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and an increase in malondialdehyde (MDA) level in the hippocampus of ethanol and LNS co-exposed animals as compared with individual exposure of ethanol and LNS. While each factor independently produced similar outcomes, the results indicate that the dual exposure paradigm could significantly strengthen the outcomes.