Effect of the dopa decarboxylase inhibitor MK-486 on L-dopa-induced inhibition of prolactin secretion: evidence for CNS participation in the L-dopa effects.

Abstract

The present studies were performed in order to determine whether the inhibition of prolactin (Prl) secretion which follows the systemic administration of L-dopa and its conversion to dopamine (DA) is mediated by central or by peripheral mechanisms. The effects of pretreatment with the dopa-decarboxylase inhibitor MK-486 (L-α-methyldopa-hydrazide) on the L-dopa and DA inhibition of Prl secretion and on dopa-decarboxylase activity in anterior pituitary, hypothalamus, cerebral cortex and adrenal medulla were evaluated in rats using a dose reported to cause peripheral but not central dopa-decarboxylase inhibition. I.v. infusions of DA, 1 and 10 µg/kg/min, and of L-dopa, 0.1 and 1 mg/kg/min for 15 min, suppressed plasma Prl levels as well as the Prl release response to 0.2 porcine stalk median eminence equivalents (pSME). I.p. administration of MK-486, 50 mg/kg, 30 min before the infusion of L-dopa did not alter either basal or pSME-stimulated Prl secretion or the inhibitory effect of L-dopa. Dopa-decarboxylase activity in the anterior pituitary and the adrenal medulla was completely inhibited by MK-486, while hypothalamic and cerebral cortex dopa-decarboxylase activity was reduced 85 and 84%, respectively. Since dopa conversion to DA could not have occurred peripherally in the presence of MK-486, the results indicate that the residual dopa-decarboxylase activity within the central nervous system (CNS) was capable of permitting sufficient conversion of L-dopa to DA to inhibit Prl secretion. These results provide evidence that L-dopa is capable of exerting its suppressive action on Prl secretion when its decarboxylation to DA is restricted to CNS sites.