Lead exposure potentiates the effects of NMDA on repeated learning

Several studies now suggest that Pb exposure disrupts NMDA receptor complex function, findings which may have implications for understanding the basis of Pb-induced learning impairments. To further evaluate this possibility, the behavioral properties of the glutamate agonist NMDA were compared in rats that had been chronically exposed to 0, 50, or 250 ppm Pb acetate in drinking water from weaning. Acute administration of NMDA (20-50 mg/kg IP) decreased accuracy in both the repeated acquisition (RA) and performance (P) components of this multiple schedule with a selective effect on the learning component in the second half of the session. Analyses of error patterns revealed that the disruption of RA accuracy derived from initial perseverative errors followed by errors of skipping forward and backwards in the 3-member response sequence. Response rates in both RA and P were suppressed by NMDA. Pb-exposure potentiated the accuracy-impairing effects of NMDA by further increasing the frequencies of these error classes, and likewise potentiated the rate-suppressing effects of NMDA. These findings add further support to the possible involvement of Pb with the NMDA receptor complex.