Neurobehavioral Effects of Neonatal Methylmercury Exposure: Impacts on Perseveration and Learning

Abstract

Neural changes occurring during the neonatal period in rodents are akin to those seen in humans during the third trimester of pregnancy. The neonatal period is a developmental period during which the monoamine systems develop so they are sensitive to external disruption. Methylmercury (MeHg), an environmental contaminant, disrupts neurobiology and behavior following exposure during various developmental periods but the neonatal period has not been modeled, partly because breast milk is a poor source of bioavailable methylmercury. To examine this developmental period, male Long-Evans rats were exposed to 0, 80, or 350 µg/kg/day MeHgCl from postnatal days 1 to 10, the rodent neonatal period. As adults, behavioral flexibility, attention, memory and expression of the dopamine transporter, DAT, in these rats was assessed. Rats exhibited changes in behavioral flexibility assessed in a spatial discrimination reversal procedure. Those rats exposed to 350 µg/kg/day MeHgCl more quickly transitioned in responding on the new lever on the second reversal and more slowly made this transition on the third reversal. Rats exposed to this dose also acquired responding in the absence of a signal more slowly, and to a lesser degree, during acquisition of the attention/memory procedure but neither attention nor memory were affected once the task was acquired. Finally, DAT expression in the striatum, PFC, and hippocampus was unchanged in these adult rats. The results of this study replicate the trend of findings seen with exposure during gestation or during adolescence.