Regional brain distribution of d-amphetamine in lead-exposed rats

The present study was designed to examine the time course of distribution of d -[ 3 H]amphetamine ( d -amph) in various brain regions and plasma in lead-intoxicated rats. Measurements of d -amph-induced locomotor activity were also recorded in these same animals. The protocol involved exposing lactating dams to either 0, 0.1, or 0.2% lead acetate Pb(Ac) 2 , in their drinking water and thus neonates indirectly to lead-contaminated milk. At weaning, control litters and half of the litters from the 0.1% Pb(Ac) 2 group were placed on distilled water while the remaining litters received the maternal regimen. Assessment of locomotor activity at 90 days of age revealed a significantly attenuated d -amph response (1.0 mg/kg, sulfate salt, sc) in the 0.2% but not in the 0.1% Pb(Ac) 2 group (both sexes). Subsequent analyses of brain d -amph distribution revealed that the 0.2% Pb(Ac) 2 group (both sexes) also had significantly decreased concentrations (10 to 12%) of d -amph in the hippocampus, striatum, and hypothalamus at 15, 30, and 90 min postinjection. Concentrations in medulla and plasma did not differ from controls. However, the time courses for the significant behavioral and radiochemical data did not coincide and correlations between d -amph concentration and locomotor activity were negligible. These data suggest that the alterations in d -amph-induced locomotor activity observed in the 0.2% Pb(Ac) 2 group animals may result in part from an inability to concentrate and/or maintain critical levels of the d -amph in specific regions in the CNS.