Rat hippocampal NMDA receptor binding as a function of chronic lead exposure level.
Chronic developmental lead (Pb) exposure is known to impair cognitive ability in children and young animals. These findings have led to research examining exposure effects on long-term potentiation (LTP), a model of synaptic plasticity, and on NMDA receptor function. This study determined the changes occurring in hippocampal 3H-MK-801 binding as a function of exposure level for comparison to changes in LTP previously reported from this laboratory. 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 solutions as their dams and maintained on these regimens until assessment as adults. A crude membrane fraction was prepared from hippocampal tissue, and Scatchard analysis conducted in the presence of saturating concentrations of glutamate 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, since increases in receptor number were uncovered, it is unlikely that changes in NMDA receptor density constitute a primary mechanism whereby Pb impairs hippocampal LTP.
Lasley
S M
SM
Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine, PO Box 1649, Peoria, IL 61656, USA. sml@uic.edu
Green
M C
MC
Gilbert
M E
ME
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007854:Lead / Q000493:pharmacokinetics / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007854:Lead; D016291:Dizocilpine Maleate