Rat hippocampal NMDA receptor binding as a function of chronic lead exposure level

Chronic developmental lead (Pb) exposure is known to impair cognitive abili ty in children and young animals. These findings have led to research exami ning exposure effects on long-term potentiation (LTP), a model of synaptic plasticity, and on NMDA receptor function. This study determined the change s occurring in hippocampal H-3-MK-801 binding as a function of exposure lev el for comparison to changes in LTP previously reported from this laborator y. Dams were exposed to 0.1%, 0.2%, 0.5% and 1.0% Pb in the drinking water beginning at parturition, and male offspring were weaned to the same soluti ons as their dams and maintained on these regimens until assessment as adul ts. a crude membrane fraction was prepared from hippocampal tissue, and Sca tchard analysis conducted in the presence of saturating concentrations of g lutamate and glycine. NMDA receptor density was elevated as a result of Pb exposure with significant increases in the 0.2% (38%) and 0.5% (30%) groups compared to control group values. No changes were observed in the 0.1% and 1.0% animals, thus constituting a biphasic dose-effect relationship. These findings are an approximate reflection of analogous relationships reported for hippocampal LTP and glutamate release, suggesting that the diminished glutamate release is one cause of the receptor up-regulation. However, sinc e increases in receptor number were uncovered, it is unlikely that changes in NMDA receptor density constitute a primary mechanism whereby Pb impairs hippocampal LTP. (C) 2001 Elsevier Science Inc. All rights reserved.