Small dose of domperidone potentiated the effects of TRH and serotonin on prolactin release in ovariectomized, estrogen-treated rats

A transient antagonism of the dopaminergic action by using a dopamine antagonist, domperidone, plus a dopamine agonist, CB154, has been shown to potentiate the effect of thyrotropin-releasing hormone (TRH) on prolactin (PRL) secretion. In order to test whether the serotonin (5-HT)-induced PRL secretion can also be enhanced in a similar way, we used 5-HT instead of TRH in our first experiment. We found that the dose of domperidone used (10 micrograms/rat) seems to be excessive since it induced a marked and substantial increase in PRL release and the use of CB154 further masked the action of 5-HT. We used a smaller dose of domperidone (1 microgram/rat) without the CB154 and found that it induced a moderate amount of PRL release which lasted for over 1 h. Given TRH (1 microgram/rat) or 5-HT (0.3 mg/rat) 1 h later resulted in a significant increase in plasma PRL which was much higher than that induced by TRH or 5-HT alone. The potentiating effect of domperidone was even more significant for the 5-HT- than the TRH-stimulated PRL secretion. Pretreatment with 5-HT or vasoactive intestinal polypeptide (10 micrograms/rat) were without any effect in potentiating the action of TRH. In conclusion, antagonizing the dopamine action appears to enhance the stimulatory effect of TRH and 5-HT on PRL secretion.