ToxSci Advance Access originally published online on July 27, 2005
Toxicological Sciences 2005 87(2):469-482; doi:10.1093/toxsci/kfi269
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Interactions of Chronic Lead Exposure and Intermittent Stress: Consequences for Brain Catecholamine Systems and Associated Behaviors and HPA Axis Function
* Environmental and Occupational Health Sciences Institute, a Joint Institute of the Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey and Rutgers University, 170 Frelinghuysen Road, Piscataway, New Jersey 08854, and Department of Environmental Medicine, Box EHSC, University of Rochester School of Medicine, Rochester, New York 14642
Received June 3, 2005; accepted July 18, 2005
Elevated lead (Pb) burden and high stress levels are co-occurring risk factors in low socioeconomic status (SES) children. Our previous work demonstrated that maternal Pb exposure can permanently alter hypothalamic-pituitary-adrenal (HPA) axis function and responsivity to stress challenges in offspring. The current study sought to determine the consequences of chronic Pb exposures initiated later in development combined with variable intermittent stress challenges. Male rats were exposed chronically from weaning to 0, 50, or 150 ppm Pb acetate drinking solutions (producing blood Pb levels of <5, 9–15, and 23–27 µg/dl, respectively). Pb itself decreased basal plasma corticosterone, with greater effects at 50 than 150 ppm; 150 ppm reduced both cytosolic and nuclear glucocorticoid receptor binding. Responsivity to stress challenges including novelty, cold, and restraint, was measured as changes in Fixed Interval (FI) schedule-controlled behavior in a subset of rats within each group. FI performance was modified by novelty stress only in Pb-treated rats, whereas cold and restraint stress effects were comparable across groups. Novelty elevated corticosterone equivalently across groups, but cold stress markedly increased corticosterone only in Pb-treated groups. The pattern of Pb-induced changes in serotonin (5-HT) or its metabolite 5-HIAA in frontal cortex, nucleus accumbens, striatum, and hypothalamus resembled that observed for basal corticosterone levels indicating a relationship between these variables. In addition to suggesting the potential for HPA axis-mediated effects of Pb on the central nervous system, these findings also raise questions about whether single chemicals studied in isolation from other relevant risk factors can adequately identify neurotoxic hazards.
Key Words: lead; stress; HPA axis; catecholamines; corticosterone; Fixed Interval.
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