A model of early life, episodic lead exposure of less than 60 ug/dl blood lead (PbB), superimposed on chronic lead exposure of about 30 ug/dl for the first year and 15 ug/dl for the remainder of life, is proposed for study in the rhesus monkey. These PbB levels are pertinent to many cases of human episodic childhood lead exposure followed by PbB levels generally seen in humans. Cohort controls not administered lead are being carried in parallel (about 5 ug/dl PbB). Monkeys exposed to higher pulse-chronic lead, without lead after the first year (Exp. III), showed a permanent deficit on Delayed Spatial Alternation (DSA) when stabilized at control PbB levels and tested as adults at 5-8 years of age. Monkeys exposed only to this high chronic lead level for the first year (no pulse and no lead after the first year: Exp. II and V) exhibited a marginal DSA facilitation as adults. Finally, monkeys exposed only at chronic PbB of 13-15 ug/dl for life showed a DSA deficit when tested at about 8 years of age (Rice et al., 1985). Chronic L-dopa treatment normalized the DSA deficit seen in the pulse-chronic animals (Exp. III) while cholinergic drugs had no differential effect on lead groups. Thus, evidence suggests that these DSA effects (facilitation at lower dose-duration lead exposure and deficits at higher dose-duration exposures) may be explained by sensory inattention resulting from damage to the dopaminergic systems of the caudate nucleus, induced in a dose- dependent manner by lead exposure during and after postnatal development in the monkey. The present grant provides for exposure conditions which the data strongly indicate will induce a DSA deficit as the monkeys develop to adulthood. These animals will be tested longitudinally to confirm if DSA facilitation is seen first, with mild toxicity, and to confirm the later stage of toxicity at which the DSA deficit finally develops. Then, additional neurochemical mechanism studies will be done on the DSA deficit. Also attentional tasks will be administered, to confirm if lead toxicity produces the postulated attention deficit, and if this correlates with the stages of DSA effects. These attentional tasks should show steadily increasing deficits from the beginning, as the stage of lead toxicity advances with continued exposure. Data will also be collected on neurochemical measures, utilizing CSF taps, to determine if the postulated dopaminergic damage occurs, and if other neurotransmitter catabolite effects are seen.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES001062-13
Application #
3249479
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1978-05-01
Project End
1989-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
13
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Ferguson, S A; Kraemer, G W; Bowman, R E et al. (1993) Lack of effect of chronic developmental lead treatment on biogenic amines and metabolites in monkey cerebrospinal fluid. Neurotoxicol Teratol 15:229-35
Ferguson, S A; Medina, R O; Bowman, R E (1993) Home cage behavior and lead treatment in rhesus monkeys: a comparison with open-field behavior. Neurotoxicol Teratol 15:145-9
Levin, E D; Schantz, S L; Bowman, R E (1992) Use of the lesion model for examining toxicant effects on cognitive behavior. Neurotoxicol Teratol 14:131-41
Ferguson, S A; Bowman, R E (1992) Effects of arecoline and scopolamine on open field behavior of adult monkeys treated with lead during the first year postpartum. Neurotoxicol Teratol 14:73-80
Laughlin, N K; Bushnell, P J; Bowman, R E (1991) Lead exposure and diet: differential effects on social development in the rhesus monkey. Neurotoxicol Teratol 13:429-40
Ferguson, S A; Bowman, R E (1990) A nonhuman primate version of the open field test for use in behavioral toxicology and teratology. Neurotoxicol Teratol 12:477-81
Ferguson, S A; Bowman, R E (1990) Effects of postnatal lead exposure on open field behavior in monkeys. Neurotoxicol Teratol 12:91-7
Franks, P A; Laughlin, N K; Dierschke, D J et al. (1989) Effects of lead on luteal function in rhesus monkeys. Biol Reprod 41:1055-62
Levin, E D; Bowman, R E (1988) Long-term effects of chronic postnatal lead exposure on delayed spatial alternation in monkeys. Neurotoxicol Teratol 10:505-10
Levin, E D; Schneider, M L; Ferguson, S A et al. (1988) Behavioral effects of developmental lead exposure in rhesus monkeys. Dev Psychobiol 21:371-82

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