Abstract
Long‐term deficits in cognitive function are the principal effects of lead (Pb^2+^) exposure in children and can be modeled in experimental animals. Current therapeutic approaches in the treatment of childhood Pb^2+^ intoxication are not effective in reversing learning deficits once they have occurred. We report that environmental enrichment reverses long‐term deficits in spatial learning produced by developmental Pb^2+^ exposure in rats. Enhanced learning performance of Pb^2+^‐exposed animals reared in an enriched environment was associated with recovery of deficits in __N‐__methyl‐D‐aspartate receptor subunit 1 (NR1) mRNA and induction of brain‐derived neurotrophic factor (BDNF) mRNA in the hippocampus. The effect of environmental enrichment on NR1 and BDNF gene expression was specific to Pb^2+^‐exposed animals and was present in the absence of changes in the NR2B subunit of the __N‐__methyl‐D‐aspartate receptor, GluR1, αCamKII, or PSD‐95 gene expression measured in the same animals. Our findings demonstrate that the learning impairments and NR1 subunit mRNA deficits resulting from developmental Pb^2+^ exposure are reversible if the animals are provided with an enriched environment even after the exposure has occurred. We propose environmental enrichment as a basis for the treatment of childhood Pb^2+^ intoxication.