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Schedule-controlled behavior in infant and juvenile monkeys exposed to lead from birth
1Toxicology Research Division, Health and Welfare Canada, Ottawa, Ontario.
Insights
Lead exposure in infant monkeys (Macaca fascicularis) altered behavior, increasing pauses in fixed ratio tasks and variability in fixed interval tasks, despite no overt toxicity signs.
Area of Science:
- Neuroscience
- Toxicology
- Primate Behavior
Background:
- Lead acetate exposure in early development can impact neurobehavioral outcomes.
- Non-human primates offer a valuable model for studying developmental neurotoxicity due to physiological similarities with humans.
Purpose of the Study:
- To investigate the long-term neurobehavioral effects of early-life lead exposure in cynomolgus monkeys (Macaca fascicularis).
- To assess the impact of lead acetate on operant conditioning performance across different developmental stages.
Main Methods:
- Infant cynomolgus monkeys were orally administered lead acetate (2000 micrograms/kg/day) from birth.
- Behavioral testing included fixed ratio (FR) and fixed interval (FI) schedules of reinforcement starting at 60 days of age.
- Performance was evaluated at infant and juvenile stages, including a multiple fixed interval-fixed ratio schedule at three years of age.
Main Results:
- Lead-treated monkeys exhibited increased post-reinforcement pause on FR schedules and decreased pause time on FI schedules during infancy.
- Juvenile lead-exposed monkeys showed increased FI run rate, pause time, and index of curvature.
- Elevated performance variability within and between sessions was observed in treated monkeys across multiple measures.
Conclusions:
- Early-life lead exposure in monkeys induces significant and lasting alterations in operant behavior.
- These behavioral changes suggest subtle neurodevelopmental disruptions even in the absence of overt clinical signs of toxicity.
- The study highlights the utility of primate models for understanding the complex behavioral consequences of developmental lead exposure.
Abstract:
Monkeys (Macaca fascicularis) were dosed orally from birth with 0 or 2000 micrograms/kg/day of lead as lead acetate. Blood lead concentrations of treated monkeys peaked at an average of 115 micrograms/dl by 100 days of age, and decreased to a steady state level of 33 micrograms/dl after withdrawal from infant formula at 270 days of age. No overt signs of toxicity were observed. Beginning at 60 days of age, monkeys were tested on a fixed ratio (FR) schedule of reinforcement, followed by a fixed interval (FI) schedule. Infants were tested in their home cages for 16 hours each day. When these monkeys reached three years of age, performance on a multiple fixed interval-fixed ratio schedule was evaluated. Infant performance was characterized by increased FR pause and decreased FI pause in the treated monkeys. Juvenile performance of lead-treated monkeys was characterized by increased Fl run rate, pause time, and index of curvature. Treated monkeys exhibited increased variability of performance both within and between sessions on several measures of Fl and FR performance.