Low-level lead exposure selectively enhances dopamine overflow in nucleus accumbens: An in vivo electrochemistry time course assessment

Abstract

Exposures to even very low levels of lead (Pb) alter behavioral and neurochemical functions. The current study was based on the hypothesis that excess synaptic dopamine (DA) availability may contribute to such disturbances and that the mesolimbic DA projection is more sensitive than the nigrostriatal system to Pb induced DA-based alterations. In vivo electrochemical measurements of potassium chloride-evoked DA overflow and clearance were compared in dorsal striatum (STR) (nigrostriatal system) and nucleus accumbens (NAC) (mesolimbic system) of male rats after 11 weeks or 11 months of postweaning exposure to 0, 50, or 150 ppm Pb acetate drinking solutions. Pb increased evoked DA overflow selectively in NAC, with biphasic effects at 11 weeks, including increases greater than 400% at 50 ppm and concentration-related effects up to 265% of control at 11 months. Considered relative to 11-week control levels, continued exposure tended to attenuate the magnitude of Pb-related increases in DA overflow in NAC. Pb decreased clearance time in both brain regions, with these effects markedly augmented across time. These changes in DA function were observed at blood Pb values of only 15-16 μg/dl, underscoring their environmental relevance. The current findings support the hypothesis of excess DA availability as a mechanism of Pb-induced behavioral alterations and of a particular vulnerability of mesolimbic DA systems (NAC) to such effects. They also suggest that different mechanisms underlie Pb-related changes in amplitude and clearance and confirm previous reports of regional differences of DA systems in response to Pb exposure.