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Maternal Lead Exposure Produces Long-Term Enhancement of Dopaminergic Reactivity in Rat Offspring

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Abstract

To determine the effect of prenatal lead exposure on brain monoaminergic systems, pregnant rats were given tap water containing 250 ppm lead acetate, for the duration of pregnancy, while tap water without lead (Pb2+) was substituted at birth. Control rats were derived from dams that consumed tap water during pregnancy, and had no exposure to lead afterwards. At 12 weeks after birth, Pb2+ content of brain cortex was increased 3- to 4-fold (P < 0.05). At this time the endogenous striatal levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid were 19% lower in Pb2+ exposed rats (P < 0.05), while there was no change in the striatal level of dopamine (DA), noradrenaline, 3,4-dihydroxyphenylglycol, serotonin (5-HT) and 5-hydroxyindoleacetic acid (HPLC/ED). Also there was no change in these monoamines and metabolites in the prefrontal cortex of Pb2+ exposed rats. However, turnover of 5-HT in prefrontal cortex, as indicated by 5-hydroxytryptophan accumulation 30 min after acute treatment with the decarboxylase inhibitor NSD-1015 (100 mg/kg IP), was lower in the Pb2+ exposed rats. In the striatum AMPH-induced (1 mg/kg IP) turnover of DA, evidenced as L-DOPA accumulation after NSD-1015, was increased to a lesser extent in the Pb2+ exposed rats (P < 0.05). The nitric oxide synthase inhibitor 7-nitroindazole (10 mg/kg IP) attenuated the latter effect, indicating that neuronal NO mediates this AMPH effect, at least in part. Moreover, DA D2 receptor sensitivity developed in Pb2+ exposed rats, as evidenced by enhanced quinpirole-induced yawning activity and enhanced quinpirole-induced locomotor activity (each, P < 0.05). These findings indicate that ontogenetic exposure to lead can have consequences on monoaminergic neuronal function at an adult stage of life, generally promoting accentuated behavioral effects of direct and indirect monoaminergic agonists, and related to increased dopamine turnover in basal ganglia.

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Acknowledgment

This study was supported by grant 2 PO5D 066 27 from the Ministry of Education and Science, Warsaw, Poland.

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Authors and Affiliations

  1. Department of Pharmacology, Medical University of Silesia, 41-808, Zabrze, Poland

    Grażyna Szczerbak, Przemysław Nowak & Ryszard Brus

  2. Department of Pharmacology, Quillen College of Medicine, East Tennessee State University, PO Box 70,577, Johnson City, TN, 37614, USA

    Richard M. Kostrzewa

Authors
  1. Grażyna Szczerbak
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  2. Przemysław Nowak
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  3. Richard M. Kostrzewa
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  4. Ryszard Brus
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Correspondence to Richard M. Kostrzewa.

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Special issue dedicated to Dr. Moussa Youdim.

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Szczerbak, G., Nowak, P., Kostrzewa, R.M. et al. Maternal Lead Exposure Produces Long-Term Enhancement of Dopaminergic Reactivity in Rat Offspring. Neurochem Res 32, 1791–1798 (2007). https://doi.org/10.1007/s11064-007-9306-0

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  • DOI: https://doi.org/10.1007/s11064-007-9306-0

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