title: Domperidone stimulates prolactin secretion in rats with complete destruction of the mediobasal hypothalamus.
abstract: The main objective of this study was to further elucidate the functional relationship between endogenous dopamine and the prolactin (PRL)-releasing effect of the dopamine antagonists domperidone and haloperidol. We studied the effect of the above dopamine antagonists on the PRL secretion in control and mediobasal hypothalamus (MBH)-lesioned rats. Significant increase in basal plasma PRL levels was detected 7 days after complete surgical destruction of the MBH. Haloperidol injection (0.5 mg/kg, i.v.) was followed by an increased plasma PRL concentration in the sham-operated animals; however, in the MBH-lesioned rats where the basal PRL levels were high haloperidol failed to produce additional PRL release. In contrast to haloperidol, domperidone (0.1 mg/kg, i.v.) was able to further elevate the MBH-lesion induced high plasma PRL concentration. Moreover, the change in plasma PRL levels of the MBH-lesioned rats was parallel with that in the sham-lesioned animals after domperidone injections. When haloperidol was given prior to the domperidone injection it did not influence the PRL releasing effect of domperidone in MBH-lesioned animals. The PRL stimulatory effect of domperidone (0.3 mg/kg, i.v.) in MBH-lesioned rats was antagonized by dopamine (20 micrograms/kg, i.v.) and bromocryptine (20 micrograms/kg, i.v.). The above results suggest that the stimulatory effect of domperidone on the pituitary PRL secretion is mediated--at least in part--through the pituitary D2 dopamine receptors, but not by the displacement of endogenous dopamine originating from the MBH and reaching the pituitary via portal vessels.
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: D T
authors.initials: DT
authors.lastname: Kiem
authors.forename: G M
authors.initials: GM
authors.lastname: Nagy
authors.forename: I
authors.initials: I
authors.lastname: Barna
authors.forename: G B
authors.initials: GB
authors.lastname: Makara
mesh_terms: D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D004294:Domperidone / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004347:Drug Interactions; D006220:Haloperidol / Q000494:pharmacology*; D007033:Hypothalamus, Middle / Q000502:physiology*; D008297:Male; D011388:Prolactin / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018492:Dopamine Antagonists; D001971:Bromocriptine; D004294:Domperidone; D011388:Prolactin; D006220:Haloperidol; D004298:Dopamine