Enhanced Stimulus Sequence-­‐Dependent Repeated Learning in Male Offspring After Prenatal Stress Alone or in Conjunction with Lead Exposure

DEBORAH A CORY-­‐SLECHTA, PHD; MIRIAM B VIRGOLINI, PHD; SUE LIU; DOUGLAS WESTON

NEUROTOXICOLOGY

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2012

0161-813X

Both lead (Pb) exposure and prenatal stress (PS) can produce cognitive deficits,and in a prior study we demonstrated enhanced cognitive deficits in repeated learning offemale rats exposed to both of these developmental insults (Cory-Slechta et al., 2010).However, PS can also lead to improved cognitive outcomes that are both gender-andcontext-dependent. Thus, the current study examined whether Pb ± PS likewise producedrepeated learning deficits in males, either after maternal or lifetime Pb exposure.Repeated learning was evaluated using a multiple schedule of repeated learning andperformance that required learning 3-response sequences in male offspring that had beensubjected to either maternal Pb (0 or 150 ppm) or lifetime Pb exposure (0 or 50 ppm)beginning two mos prior to dam breeding, to prenatal immobilization restraint stress(gestational days 16-17), or to both Pb and PS. Blood Pb, corticosterone, hippocampalglucocorticoid receptor density and brain monoamines were also measured. In contrast tooutcomes in females, sequence-specific enhancements of repeated learning accuracy wereproduced by PS, particularly when combined with Pb, results that appeared to be morerobust in combination with lifetime than maternal Pb exposure. A common behavioralmechanism of these improvements appears to be an increase reinforcement densityassociated with increased response rates and shorter session times seen with PS ± Pb thatcould both shorten time to reinforcement. Trends towards lower levels of nucleusaccumbens dopamine activity seen after both maternal Pb and lifetime Pb combined withPS suggest a possible role for this region/neurotransmitter in enhanced accuracy, whereasPS ± Pb-induced corticosterone changes did not exhibit an obvious systematicrelationship to accuracy enhancements. While PS ± Pb-based increases in accuracyappear to be an improved outcome, the benefits of increased response rate are by nomeans universal, but highly context-dependent and can lead to adverse behavioral effectsin other conditions.