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Rats exposed to lead via the maternal milk were tested at maturity on three different visual discrimination tasks. Starting at parturition the dams were given either tap water, 0.20% sodium acetate, 0.02% lead acetate, or 0.20% lead acetate in the drinking water. At weaning, the pups from all the groups were placed on normal chow and tap water. At 20 days of age, the concentration of lead in the blood and brain of the high lead-exposed offspring was approximately 6 times that of controls (11 microgram% vs 66 microgram%). A significant deficit was found in the ability of the high lead-exposed group to acquire a simultaneous visual discrimination task conducted in an operant chamber. No significant differences were observed in the ability of lead-exposed rats to acquire either a successive visual discrimination task or a cued go/no-go discrimination. Thee results suggest that early lead exposure can affect certain behavioral processes and that the effects may persist even after the rat has reached maturity.

Rats exposed to lead via maternal milk were tested at various stages of development on a number of behavioral tasks. Beginning at paturition, the dams were given either tap water, 0.02%, or 0.10% lead acetate in the drinking water. Pups from all three groups were weaned to normal chow and tap water at 21 days of age. The mean lead concentration of the dam's blood and of neonatal (20 days of age) brain and blood were all below 50 microgram/100 ml. No significant differences were found between the high lead-exposed group and controls in general as measured by wheel running over a 21 day period beginning at 30 days of age. However, there was a significant difference in wheel running behavior during the first three hr of testing. Both lead-exposed groups were found to display significantly less aggressive behavior as measured by the shock-elicited aggression test. Low level lead exposure had no discernable effect on the acquisition and subsequent reversal of a successive brightness discrimination task. Lead exposure under these conditions appears to affect some aspects of emotional behavior, while having little effect on general activity or cognitive function.

Neonatal rats were given aqueous lead acetate intragastrically from d 2--20 of life at doses of 0, 25, 75, and 225 mg Pb/kg.d. Blood Pb concentrations on d 21 were (mean +/- SE) 27 +/- 4 (control), 150 +/- 26, 263 +/- 63, and 518 +/- 97 microgram/100 ml, respectively. Growth was significantly depressed only in animals given the highest dose of Pb (225 mg/kg.d). Hematocrits were significantly decreased by d21 at all doses of Pb. Malondialdehyde (MDA) formation in 750 x g (10 min) brain supernatants induced spontaneously by aerobic incubation at 37 degrees C was not altered by Pb on d 7 and 14, but a slight decrease was observed on d 21. The extent of MDA formation induced by enzymatically generated superoxide anion was not altered by Pb toxicity during the first 21 d of life. Addition of Pb to 750 x g (10 min) brain supernatants in vitro significantly decreased MDA formation at Pb concentrations of 10(-5) M and higher. These results show that the central nervous system toxicity of Pb in neonatal rats is not associated with accelerated in vitro lipid peroxidation of brain tissue.

Inorganic lead produces cerebral dysfunction and clinically definable encephalopathies in man. To date there have been few studies on the biochemical changes in brain following exposure to inorganic lead. Studies correlating toxicity with behavioral and brain neurochemical changes following lead exposure have been hindered because adult laboratory animals are resistant to the central nervous system effects of lead poisoning. Such studies have been impeded by lack of suitable experimental models until Pentschew and Garro showed that brain lesions develop in neonatal rats when a pregnant rat newly delivered of her litter is placed on a 4% lead carbonate containing diet. Lead passes into the developing sucklings via maternal milk. Lead-poisoned new-borns have pronounced retardation of growth and during the fourth week of ilfe develop the severe signs of lead encephalopathy, namely, extensive histological lesions of the cerebellum, brain edema, and paraplegia. There is an approximate 85-fold increase in the lead concentration of both the cerebellum and cerebral cortex relative to controls, but edema and gross vascular changes are confined to the cerebellum. Ingested lead had little effect on RNA, DNA, and protein concentrations of developing rat cerebellum and cerebral cortex. However, there was a reduction of between 10 and 20% in the DNA content of the cerebellum around 3 weeks of age in the lead-exposed sucklings. This suggests a failure of cell multiplication in this part of the brain.A critical evaluation of this experimental approach indicated that under similar dietary conditions experimental lactating rats eat 30% less food than controls resulting in: (a) sustained loss in body weight of nursing mothers and that (b) offsprings who develop paraplegia and cerebellar damage do so after gaining access to lead containing diet. We have studied mothers' food consumption and body weight changes and blood, milk, and brain lead content; and newborns' body and brain weight changes, blood and brain lead content, and brain serotonin (5HT), norepinephrine (NE), dopamine (DA), and gamma-aminobutyric acid (GABA). We have found that a lactating mother rat eating 5% lead acetate (2.73% Pb) produced milk containing 25 ppm lead. When the mothers' diet is changed at day 16 from 5% PbAc to one containing 25 ppm Pb, and neonates allowed free access to the solid diet, the sucklings still have retarded body growth but do not develop paraplegia or grossly apparent vascular damage of the cerebellum. However, during the fourth week these animals exhibit a less severe form of "encephalopathy" consisting of hyperactivity, tremors, and stereotype behavior. Pair-fed controls coetaneous to experimental groups do not display such activities. There was no change in brain 5HT, GABA, or NE, but a 15-20% decrease in brain DA. Change in DA relative to other monoamines suggests a relationship between CNS dysfunction due to lead and DA metabolism in the brain.The experimental design as discribed provides a model of CNS dysfunction due to lead exposure without debilitating histopathologies. It is possible that our findings on increased motor activity and changes in brain dopamine may correspond to early responses to lead exposure before recognized overt signs of toxicity.

Daily oral administration of lead to newborn rats has no adverse effect on their body growth. Lead-treated rats were more active than age-matched controls. Endogenous levels of brain dopamine were unchanged, whereas norepinephrine was increased, suggesting a possible relationship between lead exposure during earliest developmental periods, increased motor activity, and brain norepinephrine, and not brain dopamine as previously postulated.

Neonatal rats were given aqueous lead acetate intragastrically from d 2-20 of life at doses of 0, 10, 50, and 225 mg Pb/kg.d. Blood Pb concentrations on d 21 were (mean +/- SE) 23 +/- 3 (control), 63 +/- 19, 246 +/- 55, and 994 +/- 223 microgram/100 ml, and brain Pb concentrations were 14 +/- 2, 60 +/- 5, 114 +/- 15, and 275 +/- 26 microgram/100 g, respectively. Growth was significantly depressed only in rats given the highest dose of Pb (225 mg/kg.d). Solvent-extractable lipofuscin pigment concentration of brain tissue progressively decreased over the 21-d duration of the experiment but was not significantly altered at any dose of Pb. Brain glutathione peroxidase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase activities were stimulated on d 20 at the maximal dose of Pb, but the activities of brain superoxide dismutases and catalase were not altered by Pb exposure. Locomotor activity was significantly increased in the male animals on d 20, but only at the highest dose of Pb. These results indicate that Pb toxicity in neonatal rats is not associated with accelerated in vivo lipid peroxidation in the brain, but that certain oxidant defense mechanisms in the brain are stimulated by Pb.

Newborn rats that suckled mothers eating a diet containing 4 percent lead carbonate display hyperactivity, aggressiveness, and excessive stereotyped behavior starting at 4 weeks of age. There is an eightfold increase in the concentration of lead in brain, no change in norepinephrine, but a 20 percent decrease in dopamine relative to coetaneous controls. This suggests a relationship between central nervous system dysfunction due to lead and dopamine metabolism in brain.