“Interactions of Lifetime Lead Exposure and Stress: Behavioral, Neurochemical and HPA Axis Effects”

A. ROSSI-GEORGE, M.B. VIRGOLINI, D. WESTON, M. THIRUCHELVAM AND D.A. CORY-SLECHTA.

NEUROTOXICOLOGY

ELSEVIER SCIENCE BV

Año: 2011 vol. 32 p. 83 - 99

0161-813X

Lead (Pb) and stress are co-occurring risk factors that also share biological substrates and produce common adverse effects. Correspondingly, our prior studies in rats have shown synergistic and potentiated changes in behavior, brain neurotransmitter levels and HPA axis function in offspring subjected to maternal Pb exposure and prenatal +/- offspring stress. The current study was designed to determine whether lifetime Pb exposure, consistent with human enviromental exposure, alters the profile of interactions associated with combined Pb and stress.  Dams were exposed to Pb beginning 2 mos prior to breeding (0, 50 or 150 ppm in drinking water), prenatal restraint stress (PS) on gestational days 16 and 17, or the combination. Following weaning, offspring were continued on the same Pb exposure as the dam; a subset of Pb +PS treated offspring also received 3 additional stress challenges (OS). In addition to enhancing reductions in corticosterone levels measured at the completion of behavioral testing, combined Pb + stress enhanced the reductions seen in postreinforcement pause (PRP) times on the Fixed Interval (FI) schedule in female offspring in both the 50 and 150 ppm groups, effects that were only marginal following maternal Pb + stress, consistent with a cumulative toxicity produced by lifetime Pb exposure + stress.   Changes in PRP times could indicate alterations in timing abilities or working memory as have been attributed to impulsivity, a diagnostic component of attention deficit disorder.  Consistent with reports of cortico/striatal mediation of interval timing, principal component analyses that included neurotransmitter changes and FI performance measures suggested mediation of PRP changes via altered  frontal cortex norepinephrine (NE) coupled with enhanced control by striatal monoamines.  As such, lifetime Pb exposure when combined with stress may have preferential impacts for females in the form of enhanced risk for self control/attention deficit.