Low-level lead exposure modulates effects of quinpirole and eticlopride onresponse rates in a fixed-interval schedule

Exposure to low levels of lead (Pb) results in a wide range of behavioral c hanges. These behavioral deficits of lead are modified by duration of expos ure, level of exposure, and stage of exposure. The mesoaccumbens dopamine ( DA) system appears to be critically involved in these alterations; however, the precise mechanisms are not completely understood. This study investiga ted the effects of systemic administrations of the dopamine D-2-like recept or agonist, quinpirole, and antagonist, eticlopride, on response rates of p ostweaning lead-exposed rats in a fixed-interval 1-minute (FI-1) schedule. Postweaning exposure to 50 ppm lead (lead acetate) resulted in increased re sponse rates. The dopamine D-2-like agonist, quinpirole (0.05, 1.0, 3.0 mg/ kg), reversed the effects of lead by reducing the response rates. However t he antagonist, eticlopride (0.01 and 0.05), did not produce any marked modu lation of the response rates of the lead group. Rather, systemic injections of eticlopride attenuated the response rates of control rats. The effects suggest that lead-induced alterations in FI responding are modulated by dop amine D-2-like mechanisms. Thus, postweaning, subchronic exposure to lead r esulted in enhanced sensitivity to quinpirole administration and reduced se nsitivity to eticlopride. These observations are consistent with attenuated dopaminergic activity. (C) 2001 Elsevier Science Inc. All rights reserved.