Region-specific alterations in dopamine and serotonin metabolism in brains of rats exposed to low levels of lead.
Long-term exposure to low levels of lead (Pb) has been shown to produce behavioral disturbances in humans and animal models. Additionally, these disturbances have been shown to be associated with alterations in neurotransmitter systems in certain brain regions. The study presented here was undertaken to examine the effects of low level exposure to Pb on two neurotransmitter systems in various brain regions during the postweaning period. Exposure of twenty-one day old male Long-Evans rats to 0, 25, 50, or 500 ppm Pb (as lead acetate in drinking water) for 90 days resulted in mean blood Pb levels of 4, 13, 15 and 49 micrograms/dl respectively. Similarly, this exposure protocol produced dose-dependent increases in Pb contents of various regions of brain. Frontal cortex (FC), nucleus accumbens (NA), striatum (ST), hypothalamus (HY), hippocampus (HIP) and brainstem (BS) regions were analyzed for dopamine (DA), serotonin (5HT) and their metabolites. Measurements of DA in brain regions indicated that while DA contents of NA and HY were significantly reduced by the subchronic Pb exposure, its levels in FC and HIP were not affected by the low level exposures (25 and 50 ppm) to Pb, and were actually increased by exposure to 500 ppm Pb. Dopamine metabolites, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) showed changes similar to DA. No significant changes in DA or its metabolites were observed in BS or ST in Pb-exposed animals. Serotonin content, on the other hand, showed consistent decreases in NA, FC, and BS in response to Pb with no changes in ST, HY, and HIP. Levels of the serotonin metabolite, 5-hydroxyindole acetic acid (5HIAA), were found to be decreased only in FC. These findings are of significance because the blood Pb values found at the two lower levels of Pb exposure (i.e., 25 and 50 ppm) were similar to those observed in children at risk for neurotoxicity (10-19 micrograms/dl). Additionally, these results suggest that the nucleus accumbens appears to be a preferentially susceptible area of the brain for Pb-induced neurotoxicity.
Kala
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Division of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston 77004, USA.
Jadhav
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AL
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D007854:Lead / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D051381:Rats; D012701:Serotonin / Q000378:metabolism*
D015306:Biogenic Monoamines; D007854:Lead; D012701:Serotonin; D004298:Dopamine