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, IV) 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, IV) 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, IV) in MBH-lesioned rats was antagonized by dopamine (20 μg/kg, IV) and bromocryptine (20 μg/kg, IV). 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.
- Mediobasal hypothalamic lesion
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