Susceptibility of adult rats to lead-induced changes in NMDA receptor complex function.
Because cognitive impairments can occur with occupational Pb exposures, changes in NMDA receptor complex function might be expected to occur in adult rats treated with Pb. Using drug discrimination procedures, MK-801 sensitivity was determined in adult rats at three time points: after chronic exposure to 0, 50, or 150 ppm Pb acetate; again after exposure levels were increased to 500 and 1000 ppm; and 6 months after termination of Pb exposure. Changes in blood (PbB) and brain Pb levels, and in MK-801 and CGP-39653 binding, were examined in additional groups of nonbehaviorally tested rats. Pb decreased MK-801 sensitivity after Pb exposure levels were increased, but only at 500 ppm, indicating biphasic effects and precluding any correspondence between behavioral changes and biomarkers of exposure. Associated PbBs were higher, but brain Pbs similar to those associated with MK-801 sensitivity changes following postnatal and postweaning exposures. Neither MK-801 nor CGP-39653 binding was systematically affected by chronic Pb exposure in adults. Although adult Pb exposures do produce changes in NMDA function, at least as indicated by changes in MK-801 sensitivity, vulnerability to such effects is clearly less pronounced than with exposures occurring earlier in development.
Cory-Slechta
D A
DA
Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry, NY 14642, USA.
Flaugher
C L
CL
Evans
S B
SB
Pokora
M J
MJ
Greenamyre
J T
JT
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003216:Conditioning, Operant / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000493:pharmacokinetics / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology; D007854:Lead / Q000097:blood / Q000378:metabolism; D007855:Lead Poisoning / Q000378:metabolism*; D008297:Male; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; C069052:CGP 39653; D007854:Lead; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate