title: Interactions of chronic lead exposure and intermittent stress: consequences for brain catecholamine systems and associated behaviors and HPA axis function.
abstract: 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 mug/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.
authors.affiliation: Environmental and Occupational Health Sciences Institute, a Joint Institute of the Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, 08854, USA. dcs@eohsi.rutgers.edu
authors.forename: Miriam B
authors.initials: MB
authors.lastname: Virgolini
authors.forename: Kevin
authors.initials: K
authors.lastname: Chen
authors.forename: Doug D
authors.initials: DD
authors.lastname: Weston
authors.forename: Mark R
authors.initials: MR
authors.lastname: Bauter
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Cory-Slechta
mesh_terms: D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology*; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology*; D002395:Catecholamines / Q000378:metabolism / Q000502:physiology*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007854:Lead / Q000097:blood; D007855:Lead Poisoning / Q000378:metabolism* / Q000523:psychology*; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism; D012055:Reinforcement Schedule; D013315:Stress, Psychological / Q000378:metabolism* / Q000523:psychology*
chemical_list: D002395:Catecholamines; D011965:Receptors, Glucocorticoid; D007854:Lead; D003345:Corticosterone