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The possible involvement of the dopaminergic system in the serotonin (5-HT)-stimulated prolactin (PRL) secretion was tested in this study. Adult female rats were ovariectomized for two weeks and treated with estrogen (polyestradiol phosphate, 0.1 mg/rat, sc) for 6 days before use. They either received pretreatment with alpha-methyl-p-tyrosine (250 mg/kg BW, ip), a dopamine (DA) synthesis inhibitor, or two DA antagonists, domperidone and haloperidol (0.1 mg/kg BW, iv) before receiving 5-HT (1 mg/kg BW, iv) or quipazine (1 mg/kg BW, iv), a 5-HT agonist. Blockade of DA synthesis or antagonism of DA action invariably induced elevated plasma PRL levels. 5-HT or quipazine, however, could still induce significant PRL secretion on top of the increased PRL levels. Minor difference was found between the action of domperidone and that of haloperidol. In conclusion, the dopaminergic system may not be involved in the action of 5-HT to stimulate PRL secretion.

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.

Both serotonin (5-HT) and opiates exert a stimulatory effect on PRL secretion. Some evidence suggests that the action of opiates may be elicited through serotonergic neurons. We tested this hypothesis in the present study by evaluating the effect of perturbation of the serotonergic system on PRL secretion induced by fentanyl, a potent morphine-like analgesic. Female Sprague-Dawley rats ovariectomized for 3 weeks and given polyestradiol phosphate (0.1 mg/rat) for 1 week were used in the study. Fentanyl, at a dose of 20 micrograms/rat, induced significant PRL secretion that peaked at 10 min and lasted for more than 30 min. Pretreatment with naloxone (0.5 mg/kg BW, ip) did not block the acute phase of PRL secretion, but significantly lowered the PRL level at 30 min. Fentanyl at a smaller dose (5 micrograms/rat, iv) still induced significant PRL release 10, but not 30, min after injection. This effect was significantly blocked by pretreatment with the same dose of naloxone. On the other hand, whereas animals pretreated with ketanserin or LY53857 (both at a dose of 5 mg/kg BW, ip), two specific 5-HT2 receptor antagonists, had no effect on fentanyl-induced PRL secretion, the same treatment significantly blocked 5-HT-induced PRL secretion. Likewise, pretreatment with p-chlorophenylalanine (250 mg/kg BW, ip), a 5-HT synthesis inhibitor, for 2 days had no effect on the action of fentanyl, while 5-HT-induced PRL secretion was significantly augmented. We conclude that fentanyl acts through mu-opiate receptors to stimulate PRL secretion in a process that does not involve the serotonergic system.