Da. Coryslechta, RELATIONSHIPS BETWEEN PB-INDUCED CHANGES IN NEUROTRANSMITTER SYSTEM FUNCTION AND BEHAVIORAL TOXICITY, Neurotoxicology, 18(3), 1997, pp. 673-688
Lead (Pb) exposure impairs learning and results in changes in Fixed In
terval (FI) schedule-controlled behavior in experimental animal studie
s. Studies from our laboratory suggest a major involvement of dopamine
systems, and perhaps nucleus accumbens, in the Fl performance changes
. Dopaminergic (DA) but not other classes of compounds differentially
alter Fl response rates of control and Pb-treated rats. Marked changes
in nucleus accumbens but not striatal D2 and dopamine uptake sites oc
cur in response to Pb. Further, the irreversible DA antagonist EEDQ mi
croinjected into nucleus accumbens but not into striatum suppresses Fl
performance. In contrast glutamatergic system disturbances appear to
play a key role in the learning impairments caused by Pb. Glutamatergi
c (GLU) compounds differentially alter learning accuracy levels in con
trol vs. Pb-treated rats, whereas DA compounds do not. Accuracy levels
in the learning paradigm were positively correlated with numbers of M
K-801 and glutamate binding sites in control rats; these correlations
were reversed by Pb exposure. Future studies should be designed to con
firm these relationships, to examine the brain regions involved, to de
termine the extent to which other behaviors known to be mediated by GL
U/DA mesocorticolimbic systems are disrupted by Pb, and to address the
significance of developmental period of exposure to these effects as
well as their reversibility. (C) 1997 Intox Press, Inc.