Changes in mesocorticolimbic dopamine and D1/D2 receptor levels after low level lead exposure: a time course study

Abstract

Chronic post weaning low-level lead exposure produces cognitive deficits associated with Pb-induced alterations of mesocorticolimbic dopamine (DA) function. This study examined Pb-induced changes in the temporal profile of D1/D2 receptor protein and DA levels in the nucleus accumbens (NAC), hippocampus (HIP), and the frontal cortex (FC). Male Long-Evans rats were exposed to 0 (n=16-20) and 50 ppm Pb (n=16-20) for 180 days. Blood Pb analysis by atomic absorption spectroscopy showed BPb<2 microg/dl in the control group and BPb>9 microg/dl in the Pb-exposed group. Brain DA levels were evaluated by high performance liquid chromatography; D1/D2 receptor expressions, by autoradiographic analysis. Pb exposure produced a transient hyperdopaminergic state, followed by a sustained decline in dopaminergic function within the NAC and a longer-lasting hyperdopaminergic condition within the HIP, whereas it decreased FC D1/D2 without significantly affecting FC DA levels. These findings indicate that time plays a critical, region-specific role in Pb's effects on the normal synaptic profile of the mesocorticolimbic dopaminergic system.