US EPA

10299271 

Journal Article 

Abstract 

Delineating behavioral domains underlying lead-induced cognitive deficits 

Cory-Slechta, D 

2010 

1 

Neurotoxicology and Teratology
ISSN: 0892-0362
EISSN: 1872-9738 

32 

4 

497 

English 

10.1016/j.ntt.2010.04.005 

BCI:BCI201000456220 

Association between environmental lead (Pb) exposure and IQ reductions in children have been reported in several longitudinal studies. Delineating the specific behavioral domains accounting for these IQ reductions is critical both for understanding specific mechanisms of Pb effects and for advancing behavioral therapeutic strategies. Experimental studies in Pb-exposed rats and primates established the involvement of deficits primarily in domains of learning and attention. For learning, these were reflected in paradigms that included repeated learning and discrimination reversal learning, and, for attention, in fixed ratio waiting for reward performance and fixed interval schedule-controlled behavior. Such findings indicated learning/executive impairments produced at least in part by increased perseverative and impulsive behaviors. Further mechanistic support for these behavioral deficits was provided in experimental animal studies showing adverse effects of Pb exposure on mesocorticolimbic systems of the brain, and by the ability to mimic Pb effects on learning in rats via blockade of glutamatergic receptors in nucleus accumbens. Corresponding behavioral deficits in learning and planning in particular, were seen in Pb-exposed children in the Rochester Cohort study using parallel paradigms from the CANTAB battery, with subsequent analyses of these Pb effects also showing gender and genetic differences in vulnerability. Experimental animal studies have now shown that Pb-induced learning impairments can be synergistically enhanced by maternal stress. Collectively, these studies underscore the power of backward and forward translation in advancing understanding of Pb, as well as the critical need to evaluate Pb effects in the context of other modifying factors that can enhance risk. 

34th Annual Meeting of the Neurobehavioral-Teratology-Society/50th Annual Meeting of the Teratology-Society/23rd Annual Meeting of the Organization-of-Teratology-Information-Specialists 

Louisville, KY 

June 26 -30, 2010