Effects of sustained hyperprolactinemia inducedby chronic treatment with domperidone on central dopaminergic systems in the rat

Abstract Chronic treatment with Domperidone (DOM) had no effect on basal prolactin (PRL) secretion or basal levels of Dopamine (DA) metabolites in basal hypothalamus and striatum as compared with the vehicle treated rats. Animals chronically treated with DOM did not present tolerance to a challenge dose of Haloperidol (HAL) and DOM either measuring PRL secretion or striatal DA metabolite levels. The PRL-induced incrase in hypothalamic 3,4-dihydroxyphenylacetic acid (DOPAC) was reduced. These results were accompained by no change at striatal DA receptors, a slight reduction in density-affinity at hypothalamic DA receptors but clear-cut modification in pituitary DA receptors with the appearance of a high affinity-low capacity binding sites. It can be surmised that sustained hyperprolactinemia may induce tolerance in hypothalamic Tuberoinfundibular (TIDA) neurons involved in the inhibitory control of PRL secretion and a change in the kinetic properties of pituitary DA receptors, but it does not consistently affect the activity of the nigro-striatal DA system.