The effect of dopamine antagonists and/or VIP on TRH- or VIP-induced prolactin release in estrogen- and progesterone-treated ovariectomized rats.

These experiments were conducted to test the hypothesis that the effectiveness of VIP in releasing prolactin is, like TRH, enhanced when preceded by a short period of dopamine receptor antagonism. Chronically catheterized, ovariectomized rats pretreated with estradiol benzoate and progesterone to mimic early pregnancy were used throughout these studies. In the first experiment, animals were injected either with the dopamine (DA) antagonist domperidone (DOM, 0.01 mg/rat, iv) or with vehicle (acetic acid in saline). Five minutes later, all animals were treated with the DA agonist 2-Br-alpha-ergocryptine maleate (CB-154, 0.5 mg/rat, iv) followed 60 min later by the administration of thyrotropin-releasing hormone (TRH, 1.0 micrograms/rat iv) or vasoactive intestinal peptide (VIP, 25 micrograms/rat, iv). The injection of TRH following DOM treatment increased mean plasma PRL levels 100 ng/ml above levels found in vehicle-injected rats. VIP administration, however, increased PRL levels in the blood in DOM-treated rats only 6 ng/ml above the levels in vehicle-injected animals. The same treatment protocol was used in the second experiment except that the DA antagonist, sulpiride (0.01 mg/rat, iv) was administered instead of DOM, and CB-154 was not given. In this experiment both TRH and VIP released PRL. The response to TRH, but not to VIP, was significantly greater following sulpiride than in animals treated with sulpiride vehicle. In the third experiment animals were treated with DOM, VIP, DOM plus VIP, or vehicle. Five minutes later all rats received CB-154 injections, followed 60 min later by TRH administration. The final experiment was a replicate of the third except that sulpiride was substituted for domperidone and no CB-154 was given. The resulting data revealed that (1) dopamine antagonism enhanced the effectiveness of TRH but not VIP and (2) that VIP augmented the effectiveness of DA blockade on PRL release and was additive with domperidone (but not sulpiride) on increasing the responsiveness to TRH. However, VIP administration without concurrent administration of domperidone or sulpiride did not increase the effectiveness of TRH compared to vehicle-injected animals. From these data we concluded that VIP is a PRL-releasing hormone the effect of which is not affected by interruption in dopamine tone as is observed for TRH. Second, VIP can potentiate the stimulatory actions of at least one DA receptor antagonist and TRH on PRL release. This later finding suggests that VIP may play a modulatory role in the neuroendocrine regulation of PRL secretion in the female rat.