RELATIONSHIPS BETWEEN PB-INDUCED CHANGES IN NEUROTRANSMITTER SYSTEM FUNCTION AND BEHAVIORAL TOXICITY

Authors
Citation
Da. Coryslechta, RELATIONSHIPS BETWEEN PB-INDUCED CHANGES IN NEUROTRANSMITTER SYSTEM FUNCTION AND BEHAVIORAL TOXICITY, Neurotoxicology, 18(3), 1997, pp. 673-688
Citations number
91
Categorie Soggetti
Pharmacology & Pharmacy",Neurosciences
Journal title
ISSN journal
0161813X
Volume
18
Issue
3
Year of publication
1997
Pages
673 - 688
Database
ISI
SICI code
0161-813X(1997)18:3<673:RBPCIN>2.0.ZU;2-9
Abstract
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.