Behavioural and neurochemical consequences of neonatal exposure to lead in rats

Locomotor activity, lead content and concentrations of norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in discrete brain regions were examined in rats given a fixed oral dose (50 microgram/pup) of inorganic lead from birth till weaning and then kept on water containing 80 ppm lead until either 8 or 12 weeks of age. Lead-exposed animals showed an increase (by 74 and 93 percent, respectively) in locomotor activity at 6 and 8 weeks of age. By 12 weeks, the motor activity returned to control values both in animals which were withdrawn from lead treatment at 8 weeks of age and in those continued on lead. Lead levels in brain at 8 weeks of age were highest in hypothalamus and striatum. Significant decreases in cortical NE, DA and 5-HT, mildbrain DA, striatal NE and hypothalamic DA and 5-HT were found in brains of 8 week-old hyperactive rats; in contrast, NE levels in the midbrain were elevated. Whereas the decreases in 5-HT remained unchanged, alterations in regional concentration of catecholamines were no longer evident in lead-exposed animals whose motor activity returned to normal by 12 weeks of age or in rats withdrawn from lead at age of 8 weeks. Alterations in regional levels of NE and DA appear to be associated with lead-induced increase in locomotor activity, while changes in 5-HT metabolism may result from a non-specific toxic effect of the metal.