Behavioural Effects of Low-level Developmental Exposure to Lead in the Monkey

Summary

Cynomolgus monkeys (Macaca fascicularis) dosed from birth onward with 0, 50, 100, or 500 µg/kg per day of lead had blood lead (PbB) levels of 3, 15, 25, or 55 µg/dl, respectively, before withdrawal of infant formula at 200 days of age, and later steady-state PbB levels of 3, 11, 13 or 33 µg/dl. Beginning at age 3 years these monkeys began performance on behavioural tasks designed to assess types of deficits found in children with moderate body burdens of lead, including various forms of intellectual impairment, distractibility and short attention span, and hyperactivity. The first task used here was an intermittent schedule of reinforcement, the fixed interval (FI), which required the monkey to make one response after a specified time had elapsed in order to receive a fruit juice reward. Although responding before the specified time had no consequences, monkeys (as well as other animals and humans) typically respond throughout the interval. Thus, this schedule is capable of measuring the ongoing activity of the monkey. Treated monkeys made more responses under these conditions than did control monkeys, and the effect was dose-related. Moreover, response rates for treated monkeys were more variable, both between days and even across a 50-min session, than for the control animals.

Following FI schedule testing, each monkey was tested on another intermittent schedule, the DRL (differential reinforcement of low rate), which assessed the monkey’s ability to inhibit responding. This required the monkey to wait at least 30 s before responding in order to receive a reward. Although the lead-treated monkeys were able to learn the task, they did so at a slower rate than controls and were more variable in their performance from day to day than the controls (similar to the FI results).

Short-term memory and attention were measured by two techniques: (1) delayed matching to sample, which required the monkey to remember a stimulus and signal this by choosing the correct stimulus out of three samples; and (2) a test of spatial memory, which required the monkey simply to alternate responses between two buttons, with a delay interposed between responses. On both tasks, treated monkeys were markedly deficient compared to controls.

The final task measured the monkeys’ ability to adapt to changes in the behavioural requirements of their environment. Each monkey was required to learn a series of discrimination tasks and, once learned, to learn the exact opposite task; that is, the correct answer became the incorrect, and vice-versa. Again, treated monkeys were impaired relative to controls in regard to such reversal behaviour.

These results collectively provide strong evidence for developmental exposure to lead causing behavioural impairment in the monkey, even at PbB levels near the current average for children in the United States and below presently accepted US criteria for undue risk of lead toxicity.