| Children exposed to subclinical levels of lead (Pb) early in development exhibit lasting cognitive and emotional impairments into adulthood. However, relatively little is known about the specific nature of these deficits or their neural bases. The goal of the present studies was to determine, in an animal model, the lasting effects of early, low-level Pb exposure on attention and reactivity to errors, two specific functions thought to be particularly vulnerable to this neurotoxin; and, by conducting pharmacological challenges, to examine the extent to which Pb's effects on cholinergic and GABAergic functioning contribute to the behavioral alterations. In each experiment, adult rats exposed to Pb from birth through weaning and controls were administered a visual sustained attention task in which they were required to wait for and respond to brief, unpredictable cues. Performance in all rats was disrupted on trials following an error, compared to trials following a correct response. However, the Pb-exposed animals were more disrupted by an error than were controls. In the first experiment, the muscarinic antagonist scopolamine induced, in controls, an increased reactivity to errors similar to that seen in the Pb-exposed animals without the drug, suggesting that the deficits in the Pb-exposed rats were due to cholinergic hypofunction. However, in the second experiment, administration of the anticholinesterase tacrine did not alleviate the increased reactivity to errors in the Pb-exposed rats, suggesting that the temporal or spatial patterning of cholinergic release, rather than amount of cholinergic activity, was altered by Pb exposure. The final experiment attempted to alleviate the increased reactivity to errors in the Pb-exposed animals through enhancement of GABAergic functioning. The benzodiazepine chlordiazepoxide improved attention in both treatment groups, and it eliminated the increased reactivity to errors observed in the Pb-exposed rats in the non-drug state. In conclusion, early Pb exposure increases the disruptive effect of an error, which can in turn disrupt cognitive function. These results suggest that therapeutic interventions for Pb-exposed children should not focus exclusively on cognitive rehabilitation, but should also teach children how to cope adaptively with stress or frustration. |
