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

Abstract

There is now evidence that two classes of dopaminergic receptors are present in CNS of the rat: D 1, associated, and D 2, not associated with adenylate cyclase activity. Drugs which interact specifically with D 2 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 of (−)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 woth biochemical changes. In fact, in lead exposed rats D 2 receptors, measured by (−)-[ 3H]sulpiride stereospecific binding, are altered, while D 1 receptors seem not to be affected. The alterations are different according to the area examined: D 2 receptor function is increased in the striatum and decreased in the nucleus accumbens. The impairment of D 2 receptor might explain the better capacity of substituted benzamides to improve the hyperkinetic behavior observed in lead exposed rats.