Effects of Haloperidol on Serum and Pituitary Prolactin and on Hypothalamic PIF in Rats

Abstract

At 1 h after a single subcutaneous injection of haloperidol into early proestrous rats, there was an 11-fold elevation in serum prolactin. Pituitary prolactin concentration 4 h after administration of 50 µg haloperidol/100 g BW was significantly decreased (52% of control values). In male rats, a single subcutaneous injection of 50 µg haloperidol produced an approximately 4-fold increase in serum prolactin at the end of 1 h, and a significant reduction in pituitary prolactin concentration at the end of 4 h. Hypothalamic PIF activity in male rats was reduced significantly by haloperidol whenever serum prolactin levels were elevated. These results suggest that the increased release of pituitary prolactin by haloperidol is mediated by a decrease in hypothalamic PIF activity.

Differential Time- and Dose-Dependent Effects in the Haloperidol Blockade of Luteinizing Hormone Release and Ovulation

“…The results of the second experiment confirm the report of Dickerman et al [3] that Haldol administered on the morning of proestrus is capable of blocking ovulation. Moreover, blockade of the LH surge and ovulation by the highest dose of Haldol (4.0 mg/kg) administered at 13.30 h is consistent with the suggestion of those authors of a direct action on mechanisms controlling the release of LH releas ing hormone (LHRH).…”

“…These include dibenamine and atro pine [5], reserpine and chlorpromazine [1], as well as barbi turates [4]. The neuroleptic agent haloperidol (Haldol) has also been reported to block ovulation [2,3] and to decrease hypothalamic prolactin-inhibitingandgonadotropin-releasing activity [3]. In those studies, however, the drug was ad ministered at 09.30 h on the morning of proestrus.…”

Effect of Sulphide on Plasma Prolactin in Rats

“…S injection (1 /ig/rat) into a lateral ventricle also raised plasma Prl significantly. Hypothalamic destruc tion resulted in a prominent increase of basal plasma Prl, which increased further following the injection of S. These results suggest that S stimulates Prl secretion by its possible direct action on the anterior pituitaiy.It is well known that tranquilizing drugs, including chlorpromazine, per phenazine and haloperidol, increase plasma prolactin (Prl) levels in man [Franz et al, 1970; K leinberg et al, 1971 and in rats [Ben-David et al, 1970;Lu et al, 1970], Accumulating evidence obtained from in vivo [Davis et a!., 1973;Lawson et al, 1975;Smythe et al, 1973] and in vitro studies [Dickerman et al, 1972;Lu et al, 1970 Lu et al, , 1971 suggests that these agents block the tonic inhibition of Prl release by a catecholaminergic mecha nism in the central nervous system. It has been recently reported, however, that catecholamines, especially dopamine, inhibit Prl secretion by acting not only on the hypothalamus, but also directly on the pituitary [Lu et al, 1972;Ojeda et al, 1974; Quijada et al, 1973/74].…”

The Effect of Apomorphine and Ergocriptine on the Release of MSH by the Pars intermedia of Rana pipiens

“…Prolactin in mammals, like MSH in frogs, is under inhibitory control by the hypothalamus [for review see M eites and Clemens, 1972;D onovan, 1970], Drugs increasing endogenous cate cholamine (CA) activity decrease prolactin secretion [Olivereau and Lemoine, 1973a], while drugs decreasing endogenous CAs increase prolactin secretion [Carr et a l, 1975;Gona and G ona, 1974;M acLeod, 1969], Drugs which block DA receptors increase prolactin secretion in vivo D ickerman et al, 1974;Clemens et al, 1974], Apomorphine has been found to significantly decrease prolactin secretion M artin et al. 1974] in vivo, and there is abundant evidence that ergocriptine (or the chemically similar ergocornine) substantially decreases prolactin secretion in vivo [Olivereau and Lemoine, 1973b;Smith et al, 1974;F alzon et al, 1974;Brooks and Welsch, 1974;D avies et al, 1974] and in vitro [Lu et al, 1971;M acLeod and Lehmeyer, 1974].…”