Cortical Dopaminergic Neurotransmission in Rats Intoxicated With Lead During Pregnancy. Nitric Oxide and Hydroxyl Radicals Formation Involvement

Document Type

Article

Publication Date

9-1-2008

Description

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 Pb2+ interfere with both. For this reason we investigated the effect of ontogenetic Pb2+ 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 Pb2+-induced neurotoxicity in prenatally Pb2+-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 Pb2+ 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 Pb2+ precipitated behavioral, dopamine - dependent impairments observed in mammalians.

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