EFFECTS OF SUBACUTE LEAD-EXPOSURE ON [H-3] MK-801 BINDING IN HIPPOCAMPUS AND CEREBRAL-CORTEX IN THE ADULT-RAT

We used the NMDA receptor non-competitive antagonist, [H-3]MK-801, as a ligand for an autoradiographic study to determine the effects of lea d on NMDA receptor in the rat brain. Adult male rats were administered lead acetate, 100 mg/kg, or sodium acetate, 36 mg/kg (control), by i. p. for 7 days. High lead levels were detected in blood (41.1 mu g/dl) and in brain (16.7-29.4 mu g/g). Concentrations of lead in brain regio ns were not significantly different. The [H-3]MK-801 binding was heter ogeneously distributed throughout the rat brain with the following ord er of binding densities: hippocampal formation > cortex > caudate-puta men > thalamus > brainstem. Lead exposure produced a significant decre ase in [H-3]MK-801 binding to the NMDA receptor in the hippocampal for mation including CA2 stratum radiatum, CA3 stratum radiatum, hilus den tate gyrus and presubiculum, and in the cerebral cortex including agra nular insular, cingulate, entorhinal, orbital, parietal and perirhinal areas. The hippocampal formation is known as a critical neural struct ure for learning and memory processes, whereas, cortical and subcortic al regions have been demonstrated to be involved in the modulation of complex behavioral processes. The NMDA receptor has been demonstrated to play a key role in synaptic plasticity underlying learning and memo ry. Lead-induced alterations of NMDA receptors in the hippocampal form ation and cortical areas may play a role in lead-induced neurotoxicity .