Psychopharmacological investigations of a lead-induced long-term cognitive deficit in monkeys.

This study investigated pharmacological manipulations of the cholinergic (ACh) and dopaminergic (DA) transmitter systems in monkeys with a long-term lead-induced cognitive deficit on delayed spatial alternation (DSA). Both ACh and DA have been found to be affected by developmental lead exposure and to be involved with performance on spatial learning and memory tasks. The lead-induced deficit in performance accuracy on DSA persisted throughout the 2 years of this experiment, which ended more than 8 years after the end of the postnatal lead exposure. Acute administration of agonists and antagonists of the ACh and DA systems did not elicit differential effects from the lead-exposed and control groups in terms of DSA per cent correct performance. The ACh antagonist, scopolamine, caused a dose-related decline in performance in both groups. Significant amelioration of the lead-induced DSA deficit was achieved by chronic treatment with the DA agonist, L-dopa. After withdrawal from L-dopa, the lead-related deficit reappeared. Improvement in performance of the lead-treated group was also seen after chronic amphetamine administration, but this effect was not significant. These data implicate DA mechanisms in the long-lasting cognitive effects of developmental lead exposure. The alleviation of the deficit with chronic administration of a DA precursor points to a possible line of treatment for the cognitive effects of developmental lead exposure.