Succimer chelation improves learning, attention, and arousal regulation in lead-exposed rats but produces lasting cognitive impairment in the absence of lead exposure.

Background: There is growing pressure for clinicians to prescribe chelation therapy at only slightly elevated blood lead levels. However, very few studies have evaluated whether chelation improves cognitive outcomes in Pb-exposed children, or whether these agents have adverse effects that may affect brain development in the absence of Pb exposure.

Objectives: The present study was designed to answer these questions, using a rodent model of early childhood Pb exposure and treatment with succimer, a widely used chelating agent for the treatment of Pb poisoning.

Succimer chelation normalizes reactivity to reward omission and errors in lead-exposed rats.

This study evaluated the efficacy of a 3-week course of succimer treatment to alleviate behavioral deficits in rats exposed to lead (Pb) for the first 4 weeks of life. A 3 x 2 factorial design was used: three levels of lead exposure (No Pb, Moderate, and High Pb) and two levels of chelation (succimer or vehicle). Behavioral testing was conducted following chelation therapy, from 2 to 9 months of age; this report presents the results of two of the administered tasks: (1) a conditional olfactory discrimination task (baseline task), and (2) a conditional olfactory discrimination task with periodic reward omission on some correct trials (RO task).

Reductions in blood lead overestimate reductions in brain lead following repeated succimer regimens in a rodent model of childhood lead exposure.

Although many studies have demonstrated the efficacy of succimer chelation in reducing blood and brain lead levels, the relative efficacy of the drug in the two tissues is less well understood. This issue is important because blood lead levels after chelation are used clinically to estimate reductions in the brain, the most critical organ in considering lead-induced neurotoxicity. The present study was designed to further investigate this issue, using multiple chelation regimens.