STIMULATORY EFFECT OF THE DOPA-DECARBOXYLASE INHIBITOR Ro 4-4602 ON PROLACTIN RELEASE; INHIBITION BY L-DOPA, METERGOLINE, METHYSERGIDE AND 2-Br-α-ERGOCRYPTINE

Abstract

In order to evaluate the role of serotonin (5-HT [5-hydroxytryptamine]) in the effect of L-dopa on prolactin (PRL) release, normal subjects received L-dopa alone or L-dopa plus a dopa-decarboxylase inhibitor (Ro 4-4602 [benserazide hydrochloride]) in basal conditions and following the repeated administration of metergoline, a specific anti-5-HT agent. The inhibiting effect of L-dopa on PRL levels was enhanced by metergoline. L-Dopa plus Ro 4-4602 induced a sharp increase in serum PRL levels. This effect was completely abolished by metergoline, which also significantly reduced fasting PRL levels in all the subjects studied. Ro 4-4602 alone induced a significant increase in serum PRL levels, similar to that commonly observed with chlorpromazine and TRH [thyrotropin releasing hormone]. The effect was similar in males and in females and was reproducible in experiments performed on different days. The effect of Ro 4-4602 was completely abolished by 2-Br-.alpha.-ergocryptine and metergoline, and, to a lesser degree, was reduced by methysergide. These results suggest that Ro 4-4602 is a reliable stimulus to PRL release and show that any stimulus to PRL secretion may be blocked by both dopaminergic and anti-serotonin agents.