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

Abstract

Exposure to low levels of lead (Pb) results in a wide range of behavioral changes. These behavioral deficits of lead are modified by duration of exposure, 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 investigated the effects of systemic administrations of the dopamine D 2-like receptor agonist, quinpirole, and antagonist, eticlopride, on response rates of postweaning lead-exposed rats in a fixed-interval 1-minute (FI-1) schedule. Postweaning exposure to 50 ppm lead (lead acetate) resulted in increased response 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 the antagonist, eticlopride (0.01 and 0.05), did not produce any marked modulation 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 dopamine D 2-like mechanisms. Thus, postweaning, subchronic exposure to lead resulted in enhanced sensitivity to quinpirole administration and reduced sensitivity to eticlopride. These observations are consistent with attenuated dopaminergic activity.