DIFFERENTIAL-EFFECTS OF EARLY CHRONIC LEAD-EXPOSURE ON POSTNATAL RAT-BRAIN NMDA, PCP, AND ADENOSINE-A(1) RECEPTORS - AN AUTORADIOGRAPHIC STUDY

The deleterious effects of postnatal lead (Pb) exposure on neural deve lopment, synaptic plasticity, and cognitive function have been well do cumented in laboratory animals. While the exact mechanisms by which Pb produces long-lasting neurotoxicity remain unknown, recent evidence s uggests that Pb may interact with and/or disrupt the N-methyl-D-aspart ate/phencyclidine receptor complex and the associated ion channel. In addition to perturbations of excitatory amino acid neurotransmission, chronic Pb exposure may also have deleterious effects on inhibitory me chanisms such as that provided by purinergic neuromodulation. In order to further examine the possibility that alterations of both excitator y and inhibitory neurotransmission may contribute to the neurotoxic ac tions of Pb, the effects of early Pb exposure on ligand binding to pos tnatal rat brain N-methyl-D-aspartate (NMDA), phencyclidine (PCP), and adenosine A1 receptors were examined using quantitative autoradiograp hy techniques. Rat pups nursed mothers exposed to 4% PbCO3 in their di et or a Na2CO3 control diet from postnatal day 1 (P1) to P25, At P25, rats were sacrificed and the regional distributions of brain NMDA, PCP , and adenosine A1 receptors were examined. Chronic lead exposure was found to produce a specific increase in [H-3]CGP 39653 binding to NMDA receptors in the hippocampus. [H-3]1-(1-[2-thienyl)cyclohexyl]-piperd ine ([H-3]TCP) binding to PCP receptors was largely unaffected by the chronic Pb treatment. In contrast, [H-3]cyclohexyladenosine ([H-3]CHA) binding to adenosine A1 receptors was markedly reduced in many brain regions with the largest decreases observed in the cerebellum. These r esults indicate that neonatal Pb exposure produces a specific alterati on of both excitatory and inhibitory neuromodulatory mechanisms in the postnatal rat forebrain that may underlie the behavioral hyperactivit y and increased seizure sensitivity associated with Pb neurotoxicity.