LEAD-INDUCED CHANGES IN NMDA RECEPTOR COMPLEX BINDING - CORRELATIONS WITH LEARNING ACCURACY AND WITH SENSITIVITY TO LEARNING IMPAIRMENTS CAUSED BY MK-801 AND NMDA ADMINISTRATION

This study sought to further evaluate potential mechanistic relationsh ips between Pb-induced alterations in glutamate neurotransmission and behavioral toxicity. It examined correlations between Pb-induced chang es in [H-3]MK-801 and [H-3]CGP-39653 binding sites in 4 different brai n regions (frontal cortex, dentate gyrus, CA1 and striatum) and (1) ch anges in learning accuracy on a multiple repeated acquisition and perf ormance schedule, and (2) sensitivity to the accuracy-impairing effect s of MK-801 and NMDA on this learning baseline. All data were obtained from a single population of rats that had been chronically exposed fr om weaning to 0, 50 or 250 ppm Pb acetate in drinking water and demons trated selective learning impairments and altered sensitivity to the e ffects of MK-801 and NMDA on learning accuracy. Pb exposure decreased MK-801 binding and possibly increased CGP-39653 binding, effects stati stically significant in some brain regions, but generally exhibiting s imilar trends across regions. At 0 ppm, higher levels, particularly of MK-801 binding, were associated with higher accuracy levels in the le arning paradigm and with greater decrements in learning accuracy follo wing MK-801 or NMDA administration. These linear correlations were neg ated and in some cases even reversed by 50 and 250 ppm Pb, an effect t hat might be attributable to an alteration of NMDA receptor complex su bunit composition and thus, ligand binding. Of the 4 brain regions exa mined, striatal MK-801 binding proved to be the best predictor of lear ning accuracy levels. These data provide additional support for an inv olvement of the NMDA receptor complex in Pb-induced learning impairmen ts. The fact that these effects were noted most frequently in striatum also raises the possibility that dopamine-glutamatergic interactions contribute to Pb's effects.