LOW-LEVEL LEAD-EXPOSURE SELECTIVELY ENHANCES DOPAMINE OVERFLOW IN NUCLEUS-ACCUMBENS - AN IN-VIVO ELECTROCHEMISTRY TIME-COURSE ASSESSMENT

Exposures to even very low levels of lead (Pb) alter behavioral and ne urochemical functions. The current study was based on the hypothesis t hat excess synaptic dopamine (DA) availability may contribute to such disturbances and that the mesolimbic DA projection is more sensitive t han the nigrostriatal system to Pb-induced DA-based alterations. in vi vo electrochemical measurements of potassium chloride-evoked DA overfl ow 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 p pm Pb acetate drinking solutions. Pb increased evoked DA overflow sele ctively in NAG, with biphasic effects at II weeks, including increases greater than 400% at 50 ppm and concentration-related effects up to 2 65% of control at 11 months, Considered relative to Ii-week control le vels, continued exposure tended to attenuate the magnitude of Pb-relat ed increases in DA overflow in NAG. Pb decreased clearance time in bot h brain regions, with these effects markedly augmented across lime. Th ese changes in DA function were observed at blood Pb values of only 15 -16 mu g/dl, underscoring their environmental relevance. The current f indings support the hypothesis of excess DA availability as a mechanis m of Pb-induced behavioral alterations and of a particular vulnerabili ty of mesolimbic DA systems (NAC) to such effects. They also suggest t hat different mechanisms underlie Pb-related changes in amplitude and clearance and confirm previous reports of regional differences of DA s ystems in response to Ph exposure. (C) 1998 Academic Press.