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Elsevier Science

Brain Res. 1991 Jul 05;553(1):65-74. doi: 10.1016/0006-8993(91)90231-j.

Low level lead exposure increases sensitivity to the stimulus properties of dopamine D1 and D2 agonists.

Brain research

D A Cory-Slechta, D V Widzowski

Affiliations

  1. Department of Biophysics, University of Rochester School of Medicine and Dentistry, NY 14642.

PMID: 1681979 DOI: 10.1016/0006-8993(91)90231-j

Abstract

To examine the impact of Pb exposure on dopaminergic (DA) function, weanling rats were chronically exposed to 0, 50 or 250 ppm Pb acetate in drinking water. At 3 months of age, the rats were trained to discriminate the stimulus properties of either the D1 agonist SKF38393 (3.0 mg/kg i.p.; D1/sal) or the D2 agonist quinpirole (0.05 mg/kg i.p., D2/sal) from saline using a standard two-lever operant food-reinforced drug discrimination paradigm. Lead-exposed rats learned the discriminations faster than respective controls. Moreover, they exhibited greater levels of drug lever responding to lower doses of the training drugs (D1/sal and D2/sal), and to selected doses of other direct and indirect DA agonists (D2/sal only), including apomorphine, cocaine and (+)-amphetamine, and less blockade of drug lever responding by haloperidol (D2/sal). Taken together, these findings are consistent with a generalized DA supersensitivity. There were no differential Pb effects when non-DA compounds including morphine, pentobarbital and MK-801 were substituted for the training drugs, indicating the selectivity of the DA effects in the context of these experiments, and the improbability of a non-specific behavioral causation. Pb-exposed rats in the D2/sal group also showed a pronounced enhancement of drug lever responding when NMDA was substituted for quinpirole, suggesting the possibility of a Pb-induced NMDA supersensitivity as well.

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