Preferential vulnerability of nucleus accumbens dopamine binding sites to low-level lead exposure: time course of effects and interactions with chronic dopamine agonist treatments.
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. D1-like and D2-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 D1-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 D2-like and DT sites were sustained across the 12-month exposure, whereas D1-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.
Pokora
M J
MJ
Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry, New York 14642, USA.
Richfield
E K
EK
Cory-Slechta
D A
DA
D000284:Administration, Oral; D000818:Animals; D001058:Apomorphine / Q000008:administration & dosage / Q000494:pharmacology*; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology*; D001665:Binding Sites; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D050483:Dopamine Plasma Membrane Transport Proteins; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D007700:Kinetics; D007854:Lead / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013997:Time Factors
D001552:Benzazepines; D002352:Carrier Proteins; D018491:Dopamine Agonists; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009942:Organometallic Compounds; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D007854:Lead; C071262:SK&F 82958; D001058:Apomorphine; C008261:lead acetate; D004298:Dopamine