Impacts of a perinatal exposure to manganese coupled with maternal stress in rats: Learning, memory and attentional function in exposed offspring.
The developmental effects of chemicals that co-occur in vulnerable populations with elevated psychological stress are of increasing concern to the public. To investigate these concerns, we developed a rodent model of co-occurring perinatal manipulations and conducted a series of cognitive assessments in male and female offspring. Manganese (Mn), a neurodevelopmental toxicant when exceeding physiological requirements, was delivered in the drinking water (0, 2, or 4 mg Mn/mL) of pregnant rats from gestational day (GD) 7 to postnatal day (PND) 22. A variable perinatal stress paradigm was applied to half of the animals from GD13 to PND9. Novel object recognition (NOR), Morris water maze (MWM), differential reinforcement of low-rates procedure (DRL), cued and uncued choice reaction time (CRT) tests were used to assess cognitive functions in offspring. Mn (4 mg/mL) and stress impaired NOR in adolescent males but facilitated NOR performance in females. However, when stress and Mn were combined these effects were attenuated in both sexes. During training for the DRL, Mn (2 mg/mL) facilitated, while stress impaired, lever press learning in both genders. Few treatment effects were found on DRL or MWM performances. During the CRT evaluations, Mn (2 and 4 mg/mL) and stress reduced cued attention in males, while stress reduced uncued attention in females. Mn and stress increased anticipatory responding in cued CRT in both genders, while only stress affected this measure in females during uncued CRT. Mn and stress slowed decision time in both sexes and in both CRT tests, while movement time was slowed by stress in females. For all CRT measures Mn combined with stress either eliminated the gender-specific differences and attenuated or improved the responses observed with either factor alone, depending on the concentration of Mn. The effects of perinatal stress on these cognitive functions may undermine the detection of effects due to chemical exposure and underscores the need to consider the psychological health and wellbeing of the mother and her environment in risk assessment for developmental neurotoxicity of chemicals.