Cortical dopaminergic neurotransmission in rats intoxicated with lead during pregnancy. Nitric oxide and hydroxyl radicals formation involvement.
It is well established that low level Pb-exposure is associated with a wide range of cognitive and neurobehavioral dysfunctions in children. In fact, Pb-induced damage occurs preferentially in the prefrontal cerebral cortex, hippocampus and cerebellum - the anatomical sites which are crucial in modulating emotional response, memory and learning. Previously it was also shown that nitric oxide (NO) signaling pathway as well as glutamatergic neurotransmission are both involved in brain development, neurotoxicity and neurodegeneration processes whereas Pb(2+) interfere with both. For this reason we investigated the effect of ontogenetic Pb(2+) exposure on dopaminergic neurotransmission in the medial prefrontal cortex (mPFC) of rats after amphetamine (AMPH) and/or 7-nitroindazole (7-NI) administration. Furthermore, the possible role of oxidative stress in Pb(2+)-induced neurotoxicity in prenatally Pb(2+)-treated rats was explored in the content of hydroxyl radical (HO) species in mPFC after AMPH and/or 7-NI injection, assessed by HPLC analysis of 2.3-dihydroxybenzoic acid (2.3-DHBA) - spin trap product of salicylate. As shown, the results of this study suggest that Pb(2+) exposure during intrauterine life did not substantially affect cortical dopaminergic neurotransmission in adult offspring rats evaluated by means of microdialysis of mPFC and the content of the cortical HO. It is likely that striatum, nucleus accumbens or other dopamine rich brain areas are more intricately associated with Pb(2+) precipitated behavioral, dopamine - dependent impairments observed in mammalians.
Nowak
Przemysław
P
Department of Pharmacology, Medical University of Silesia, H. Jordana 38, 41-808 Zabrze, Poland. pnowak@sum.edu.pl
Szczerbak
Grazyna
G
Nitka
Dariusz
D
Kostrzewa
Richard M
RM
Jośko
Jadwiga
J
Brus
Ryszard
R
D000661:Amphetamine / Q000633:toxicity; D000818:Animals; D000697:Central Nervous System Stimulants / Q000633:toxicity; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000633:toxicity; D005260:Female; D017665:Hydroxyl Radical / Q000378:metabolism; D007191:Indazoles / Q000633:toxicity; D007854:Lead / Q000633:toxicity*; D020263:Lead Poisoning, Nervous System / Q000378:metabolism* / Q000503:physiopathology; D017551:Microdialysis; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012459:Salicylates / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
D000697:Central Nervous System Stimulants; D004791:Enzyme Inhibitors; D007191:Indazoles; D012459:Salicylates; D007854:Lead; D009569:Nitric Oxide; D017665:Hydroxyl Radical; D000661:Amphetamine; C080122:7-nitroindazole; D004298:Dopamine