Domperidone stimulates prolactin secretion in rats with complete destruction of the mediobasal hypothalamus.
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.
Kiem
D T
DT
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
Nagy
G M
GM
Barna
I
I
Makara
G B
GB
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
D018492:Dopamine Antagonists; D001971:Bromocriptine; D004294:Domperidone; D011388:Prolactin; D006220:Haloperidol; D004298:Dopamine