Chronic lead treatment induces in rat a specific and differential effect on dopamine receptors in different brain...

There is now evidence that two classes of dopaminergic receptors are present in CNS of the rat: D1, associated, and D2, not associated with adenylate cyclase activity. Drugs which interact specifically with D2 receptor are more capable of antagonizing the hyperkinetic behavior induced by lead exposure in rat. They also have a beneficial effect in children with hyperkinetic disorders. We found that the dose (-)sulpiride which causes sedation is lower in lead intoxicated animals than in controls. On the contrary, haloperidol produces sedation with the same potency in lead-treated and in control rats. The reported behavioral effects were found to be correlated with biochemical changes. In fact, in lead exposed rats D2 receptors, measured by (-)-[3H]sulpiride stereospecific binding, are altered, while D1 receptors seem not to be affected. The alterations are different according to the area examined: D2 receptor function is increased in the striatum and decreased in the nucleus accumbens. The impairment of D2 receptor might explain the better capacity of substituted benzamides to improve the hyperkinetic behavior observed in lead exposed rats.