Impaired Spatial Learning and Reduced MK-801 Associated Behavioral Deficits in Rodents Following Early Postnatal Exposure to Low-level Lead

Abstract

The current research aimed to investigate the effects of early postnatal exposure to low-level lead on the spatial learning of Long-Evans Hooded rats tested in the Morris water maze. To explore possible neurotoxic actions of lead on the N-methyl-D-aspartate (NMDA) receptors, the non-competitive NMDA receptor antagonist (+)-5-methyl-10,11-dihydroxy-5h- dibenzo(a,d)cyclohepten-5,10-imine (MK-801) was used. Two-day-old pups were randomly assigned to 0.1% lead carbonate diet or control diet and weaned onto regular food on postnatal day (PND) 23. Spatial acquisition was assessed from PND 24 to PND 27. Thirty minutes prior to behavioral testing, rats received an intraperitoneal (i.p.) injection of 0.1% MK-801 or saline. In the saline treatment group, Pb-exposed rats exhibited significantly longer overall mean escape latencies than those on the control diet, replicating the impaired spatial learning of Pb-exposed animals tested at a young age. Although MK-801 injection severely impaired animals’ water maze performance regardless of diet, it affected the performance of Pb-exposed animals to a lesser extent than animals on the control diet. No main effects of diet and drug were found for probe trials on PND 28 and PND 36, but interestingly, lead diet/MK-801 animals performed significantly better than control diet/MK-801 animals during the first probe trial. Unfortunately, MK-801 not only caused animals to display higher activity levels in the activity box, but also significantly impaired animals’ performance in the cued trial, suggesting non-specific sensorimotor deficits induced by MK-801 treatment might be responsible for animals’ poor performance. However, a significant drug by diet interaction in the escape latencies and the significantly better probe trial performance of Pb-exposed animals within the MK-801 treatment group imply that lead exposure actually alleviated behavioral deficits induced by MK-801 injection, providing evidence for a possible interaction between lead and MK-801 at the molecular level.