Influence Of Low Level Maternal Pb Exposure On Stress Challenge Responsivity Of Prenatally-Stressed Offspring

4. VIRGOLINI, M.B.; ROSSI-GEORGE, A; WESTON, D.D.; CORY-SLECHTA, D.A.

NEUROTOXICOLOGY

Año: 2008 vol. 29 p. 928 - 939

0161-813X

We previously demonstrated potentiated effects ofmaternal Pb exposure producing blood Pb(PbB) levelsaveraging 39 mg/dl combined with prenatal restraint stress (PS) on stress challenge responsivity offemale offspring as adults. The present study sought to determine if: (1) such interactions occurred atlower PbBs, (2) exhibited gender specificity, and (3) corticosterone and neurochemical changescontributed to behavioral outcomes. Rat dams were exposed to 0, 50 or 150 ppm Pb acetate drinkingwater solutions from 2 mos prior to breeding through lactation (pup exposure ended at weaning; meanPbBs of dams at weaning were <1, 11 and 31 mg/dl, respectively); a subset in each Pb group underwentprenatal restraint stress (PS) on gestational days 16–17. The effects of variable intermittent stresschallenge (restraint, cold, novelty) on Fixed Interval (FI) schedule controlled behavior and corticosteronewere examined in offspring when they were adults. Corticosterone changes were also measured in nonbehaviorallytested (NFI) littermates. PS alone was associated with FI rate suppression in females and FIrate enhancement in males; Pb exposure blunted these effects in both genders, particularly followingrestraint stress. PS alone produced modest corticosterone elevation following restraint stress in adultfemales, but robust enhancements in males following all challenges. Pb exposure blunted thesecorticosterone changes in females, but further enhanced levels in males. Pb-associated changes showedlinear concentration dependence in females, but non-linearity in males, with stronger or selectivechanges at 50 ppm. Statistically, FI performance was associated with corticosterone changes in females,but with frontal cortical dopaminergic and serotonergic changes in males. Corticosterone changesdifferedmarkedly in FI vs. NFI groups in both genders, demonstrating a critical role for behavioral historyand raising caution about extrapolating biochemical markers across such conditions. These findingsdemonstrate that maternal Pb interacts with prenatal stress to further modify both behavioral andcorticosterone responses to stress challenge, thereby suggesting that studies of Pb in isolation from otherdisease risk factors will not reveal the extent of its adverse effects. These findings also underscore thecritical need to extend screening programs for elevated Pb exposure, now restricted to young children, topregnant, at risk, women.