Superfund Research Program
Factors Modifying Behavioral Toxicity of Lead
Project Leader: Barbara J. Strupp
Grant Number: P42ES005950
Funding Period: 1995 - 2000
- Project Summary
Final Progress Reports
Studies conducted during 1998-1999 revealed that some of the deficits that we had previously observed with a regimen that produces periweaning spiking of blood lead levels were not seen with a regimen that avoids this spiking by dramatically lowering the concentration of lead acetate in the drinking water around the time of weaning. Because the researchers still felt that it would be optimal to use this non-spiking regimen for the DMSA study if it produced lasting, robust cognitive deficits, they developed several new tasks predicted to be even more sensitive to lead-induced cognitive dysfunction than those previously used. The first two studies conducted during this past year (1999-2000) compared our spiking regimen to a non-spike regimen that produces constant postweaning BPb levels of 35-45 ug/dl. Each of these two studies included 72 animals (each from a different litter). Different cognitive tasks were included in the two studies, each lasting approximately 4 months. These studies revealed lasting cognitive impairment in animals exposed to lead from postnatal day 1-30, using the non-spiking regimen. These animals exhibited significant impairment in attentional set shifting, sustained attention, and associative ability. Many other cognitive functions were intact. It is also notable that the group exposed to Pb from PND 1-30 including periweaning spiking (the Spike Pb group) also exhibited impaired attentional set shifting and associative ability, but not impaired sustained attention. Moreover, this latter group was significantly less distractible than controls in a selective attention task. These studies provided important new information on the lasting cognitive effects produced by a short period of early lead exposure and provided sensitive dependent measures for the subsequent study to assess the ability of DMSA to prevent these lasting cognitive deficits. Finally, the researchers completed a study to assess the sensitivity of Pb-exposed and control rats to the attentional effects of chlordiazepoxide, a benzodiazepene agonist. This study revealed that a short period of early lead exposure produces lasting changes in sensitivity to the effects of this drug, suggesting lasting changes in the GABAergic modulation of attention. These data shed new light on the neural mechanism(s) that underlie lead-induced attentional changes.