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Preferential Vulnerability of Nucleus Accumbens Dopamine Binding Sites to Low‐Level Lead Exposure: Time Course of Effects and Interactions with Chronic Dopamine Agonist Treatments
Author(s) -
Pokora M. J.,
Richfield E. K.,
CorySlechta D. A.
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.67041540.x
Subject(s) - nucleus accumbens , agonist , apomorphine , dopamine , chemistry , medicine , dopamine agonist , endocrinology , putamen , caudate nucleus , dopamine receptor d1 , dopamine receptor , pharmacology , receptor , biology
This study examined the hypotheses that low‐level lead (Pb) exposure would increase dopamine (DA) binding sites, would do so preferentially in nucleus accumbens, and that such effects would be modified by concurrent DA agonist treatment. D 1 ‐like and D 2 ‐like binding sites and the dopamine transporter (DT) were measured autoradiographically in caudate‐putamen and nucleus accumbens of rats exposed from weaning to 0, 50, or 150 ppm Pb acetate drinking solutions with or without concurrent chronic intermittent intraperitoneal injections of the D 1 ‐like agonist SKF 82958 or the DA agonist apomorphine after 2 weeks (no injections), 8 months, or 12 months of Pb exposure. Pb selectively decreased DA binding in nucleus accumbens. Decreases in D 2 ‐like and DT sites were sustained across the 12‐month exposure, whereas D 1 ‐like sites evidenced recovery at 12 months. Chronic intermittent DA agonist treatments reversed these effects of Pb in nucleus accumbens, restoring receptor and DT binding levels to normal, despite decreasing binding sites of non‐Pb‐treated rats. These studies implicate increased DA availability as a mechanism of Pb‐induced DA system changes. They also raise the possibility that Pb exposure could serve as a predisposing factor in neurodegenerative diseases associated with DA system dysfunction or could alter the course of DA‐based therapeutic treatments.