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.
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