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 (Pb(2+)) 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 Pb(2+)) being substituted at birth. Control rats were derived from dams that consumed tap water throughout pregnancy, and had no exposure to Pb(2+) afterwards. At 12 weeks after birth in vivo microdialysis of the neostriatum was employed to demonstrate that maternal Pb(2+) exposure was without effect on the baseline dopamine (DA) microdialysate concentration as well as amphetamine (AMPH, 1.0mg/kg i.p.)-evoked release of striatal DA. Also, prenatal Pb(2+) exposure did not enhance AMPH- and 7-nitroindazole (neuronal nitric oxide synthase inhibitor) (7-NI, 20mg/kg i.p.)-induced hydroxyl radical (HO) formation in the striatum, as indicated by analysis of the salicylate spin-trap product 2,5-dihydroxybenzoic acid. However, in rats exposed prenatally to Pb(2+), the facilitatory effect of 7-NI on DA exocytosis was attenuated. On the basis of the current study we conclude that maternal Pb(2+) exposure distorts the dopaminergic-nitrergic interaction in the nigrostriatal pathway, but without involvement of reactive oxygen species (ROS).
Nowak
Przemysław
P
Department of Pharmacology, Medical University of Silesia, H. Jordana 38, 41-808 Zabrze, Poland. pnowak@slam.katowice.pl
Szczerbak
Grazyna
G
Nitka
Dariusz
D
Kostrzewa
Richard M
RM
Sitkiewicz
Tomasz
T
Brus
Ryszard
R
D000661:Amphetamine / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D017665:Hydroxyl Radical / Q000378:metabolism*; D007191:Indazoles / Q000494:pharmacology*; D007854:Lead / Q000008:administration & dosage / Q000633:toxicity*; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*
D015259:Dopamine Agents; D004791:Enzyme Inhibitors; D007191:Indazoles; D017382:Reactive Oxygen Species; D007854:Lead; D017665:Hydroxyl Radical; D000661:Amphetamine; C080122:7-nitroindazole; D004298:Dopamine