Effect of Prenatal Lead Exposure on Nigrostriatal Neurotransmission and Hydroxyl Radical Formation in Rat Neostriatum: Dopaminergic-Nitrergic Interaction

Document Type

Article

Publication Date

4-3-2008

Description

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 dopamine (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{radical dot}) formation in the striatum, as indicated by analysis of the salicylate spin-trap product 2,5-dihydroxybenzoic 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).

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