Effect of prenatal lead exposure on nigrostriatal neurotransmission and hydroxyl radical formation in rat neostriatum: Dopaminergic-nitrergic interaction

The present study was designed to explore the role of ontogenetic lead (Pb2+) exposure on a putative dopaminergic-nitrergic interaction in the nigrostriatal pathway. Pregnant Wistar rats were given tap water containing 250-ppm lead acetate, for the duration of pregnancy, with regular tap water (without Pb2+) being substituted at birth. Control rats were derived from dams that consumed tap water throughout pregnancy, and had no exposure to Pb2+ afterwards. At 12 weeks after birth in vivo microdialysis of the neostriatum was employed to demonstrate that maternal Pb2+ exposure was without effect on the baseline dopantine (DA) microdialysate concentration as well as amphetamine (AMPH, 1.0 mg/kg i.p.)evoked release of striatal DA. Also, prenatal Pb2+ exposure did not enhance AMPH- and 7-nitroindazole (neuronal nitric oxide synthase inhibitor) (7-NI, 20 mg/kg i.p.)-induced hydroxyl radical (HO center dot) formation in the striatum, as indicated by analysis of the salicylate spin-trap product 2,5dihydroxybenzoic acid. However, in rats exposed prenatally to Pb2+ the facilitatory effect of 7-NI on DA exocytosis was attenuated. On the basis of the current study we conclude that maternal Pb2+ -exposure distorts the dopaminergic-nitrergic interaction in the nigrostriatal pathway, but without involvement of reactive oxygen species (ROS). (c) 2008 Elsevier Ireland Ltd. All rights reserved.