NUCLEUS-ACCUMBENS DOPAMINERGIC MEDICATION OF FIXED-INTERVAL SCHEDULE-CONTROLLED BEHAVIOR AND ITS MODULATION BY LOW-LEVEL LEAD-EXPOSURE

To examine the assertion that changes in nucleus accumbens (NAC) dopam ine (DA) activity serve as a mechanism of lead (Pb)-induced disruption of fixed interval (FI) schedule-controlled behavior, the effects of i ntra-NAC administration of the irreversible DA antagonist EEDQ (N-etho xycarbonyl-2-ethoxy-1,2-dihyroquinoline) and of dopamine itself on FI performance were compared in rats that had been chronically exposed to 0, 50 or 500 ppm Pb acetate in drinking water from weaning. Pb exposu re per se (500 ppm), as in past studies, increased Fl response rates, primarily by shortening interresponse times. Although DA, which produc ed rate-dependent effects, increased FI rates at low doses in the 0 an d 50 ppm groups, it did so by decreasing postreinforcement pause times . Ail DA doses decreased rates in the 500 ppm group. In contrast, the DA antagonist EEDQ suppressed FI response rates, effects that were not strongly rate dependent, by increasing both postreinforcement pause v alues and mean interresponse times. Pb exposure (500 ppm) delayed the recovery of response rates to control levels at the highest EEDQ dose, raising the possibility of a delay in receptor production rate. Colle ctively, these data suggest that NAC DA activity may be an important m odulator of FI response rates. Enhanced NAC DA activity may contribute to Pb-associated increases in FI rates and may underlie the different ial response of control and 500 ppm Pb-treated groups to intra-NAC DA administration. The different processes by which DA and Pb increase Fl rates, however, suggests that additional mechanisms are operative in the case of Pb.