Time course of postnatal lead-induced changes in dopamine receptors and their relationship to changes in dopamine...

Although alterations in dopaminergic function represent a potential neurochemical basis of Pb-induced behavioral deficits, the impact of postnatal Pb exposure on DA systems has not been adequately delineated. This study examined the effects of postnatal Pb exposure, across a broad range of concentrations, on the ontogeny of both D1 and D2 DA (dopamine) receptors in striatum and nucleus accumbens. Rat pups were exposed to Pb from 0-21 days of age via lactating dams consuming solutions of 0, 100, 350, 1000 or 2000 ppm Pb acetate. Pups were sacrificed for homogenate receptor binding assays at 7, 14, 21 or 60 days of age. Postnatal Pb exposure generally facilitated DA receptor number (Bmax) development over the first 21 days of age, in both striatum and nucleus accumbens, without any apparent effects on receptor affinity (Kd values). Residual changes in Bmax were found for both D1 and D2 receptors at 60 days of age, with Bmax changes occurring in opposite directions in the two brain regions. D1 Bmax values were increased in striatum, and decreased in nucleus accumbens at PbB (blood lead levels) of > 50 ug/dl, whereas, at PbBs of 10-20 ug/dl, but not higher, D2 Bmax values were decreased in striatum but increased in nucleus accumbens. These findings suggest a preferential vulnerability of D2 receptors to lower Pb exposure concentrations and underscore the importance of Pb exposure level and brain region to resulting receptor changes. A linear relationship was observed between changes in nucleus accumbens D2 receptor Bmax values and Pb-induced changes in D2 sensitivity as derived from a drug discrimination study using littermates of offspring from the current study (Cory-Slechta et al., 1992), suggesting nucleus accumbens as a preferential site of Pb-induced D2-mediated effects.