TIME-COURSE OF POSTNATAL LEAD-INDUCED CHANGES IN DOPAMINE-RECEPTORS AND THEIR RELATIONSHIP TO CHANGES IN DOPAMINE SENSITIVITY

Although alterations in dopaminergic function represent a potential ne urochemical basis of Pb-induced behavioral deficits, the impact of pos tnatal Pb exposure on DA systems has not been adequately delineated. T his study examined the effects of postnatal Pb exposure, across a broa d range of concentrations, on the ontogeny of both D1 and D2 DA (dopam ine) receptors in striatum and nucleus accumbens. Rat pups were expose d to Pb from 0-21 days of age via lactating dams consuming solutions o f 0, 100, 350, 1000 or 2000 ppm Pb acetate. Pups were sacrificed for h omogenate receptor binding assays at 7, 14, 21 or 60 days of age. Post natal Pb exposure generally facilitated DA receptor number (Bmax) deve lopment over the first 21 days of age, in both striatum and nucleus ac cumbens, without any apparent effects on receptor affinity (Kd va lues ). 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/d l, whereas, at PbBs of 10-20 ug/dl, but not higher, D2 Bmax values wer e decreased in striatum but increased in nucleus accumbens. These find ings suggest a preferential vulnerability of D2 receptors to lower Pb exposure concentrations and underscore the importance of Pb exposure l evel and brain region to resulting receptor changes. A linear relation ship was observed between changes in nucleus accumbens D2 receptor Bma x values and Pb-induced changes in D2 sensitivity as derived from a dr ug discrimination study using littermates of offspring from the curren t study (Cory-Slechta et al., 1992), suggesting nucleus accumbens as a preferential site of Pb-induced D2-mediated effects. (C) 1994 Intox P ress, Inc.