Lead exposure and dorsomedial striatum mediation of fixed interval schedule-controlled behavior

Prior studies demonstrate a critical role for mesolimbic dopamine systems, particularly nucleus accumbens, in the mediation of fixed interval (FI) schedule-controlled behavior and an enhancement of nucleus accumbens dopamine activity as a mechanism of chronic postweaning lead (Pb)-induced increases in Fl response rates. Since dorsomedial striatum, like nucleus accumbens, receives limbic input, it could also conceivably contribute to Pb-related effects on FI performance. Therefore, changes in FI schedule-controlled behavior were examined following administration of dopamine or the non-specific irreversible dopamine antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) into dorsomedial striatum of rats exposed from weaning to 0, 50 or 500 ppm Pb acetate drinking solutions. The 500 ppm exposure increased baseline FI response rates relative to both 0 and 50 ppm. Intra-dorsomedial striatum EEDQ and dopamine had no effects when examined across all animals. However, both compounds produced rate-dependent effects, i.e. increases or decreases in rate in different subjects, depending upon baseline Fl overall rates. The rate-increasing effects of intra-dorsomedial striatum dopamine actually mimicked Pb effects, increasing Fl overall and run rates and shortening postreinforcement pause times. Further, Pb exposure modulated effects of dopamine and EEDQ in dorsomedial striatum. While these collective findings conceivably suggest dorsomedial striatum as another potential site through which postweaning Pb exposure influences FI performance, this possibility is not supported by other studies that show that chronic postweaning Pb alters dopamine binding sites and evoked dopamine release in nucleus accumbens but not in dorsomedial striatum even over a year exposure period. Thus, while both regions may play a role in mediating Fl performance under normal conditions, it appears that alterations in nucleus accumbens dopamine activity may be sufficient to induce chronic postweaning Pb-induced increases in FI response rates.