CORRELATION BETWEEN THE EFFECTS OF NEUROLEPTICS ON PROLACTIN RELEASE, MAMMARY STIMULATION AND THE VAGINAL CYCLE IN RATS

Abstract

The correlation between hyperprolactinaemia induced by the administration of neuroleptic drugs, disturbances of the vaginal cycle and mammary gland stimulation in rats was investigated as a test model simulating the clinical syndrome of hyperprolactinaemia and amenorrhoea with anovulation. In acute experiments in which clozapine, sulpiride and chlorpromazine were administered orally to rats of both sexes, there were rapid increases in the level of prolactin in the serum with peak values between 15 and 60 min. The responses of female rats to various doses of sulpiride were consistently higher than those of male rats. Hyperprolactinaemia induced by sulpiride in dioestrous rats failed to desensitize the ovaries to the ovulatory effect of exogenous luteinizing hormone releasing hormone. Studies of these substances and of metoclopramide, haloperidol and thioridazine were then carried out in female rats by daily oral administration over a period of 13 days. The increases in the level of prolactin in the serum were paralleled by disruption of the vaginal cycle up to and including constant dioestrus and by mammary gland stimulation which, like the preceding phenomena, showed dose-dependence. The potencies of these six neuroleptics, as estimated from their effects on the mammary gland, appeared to be haloperidol⪢ sulpiride ≥ metoclopramide = thioridazine > chlorpromazine > clozapine.