Involvement of Brain Serotonin in the Prolactin- Releasing Effect of Opioid Peptides*

The role played by brain serotonin (5-HT) neurotransmission in mediating the PRL-releasing effect of enkephalins was investigated in the rat. Both MetG-enkephalin (Metenk) and (D-Met2, Pro5)-enkephalinamide (EKNH2), an analog with long lasting analgesic activity, were used in freely moving rats bearing a cannula chronically implanted into the jugular vein. Met-enk injected intracerebroventricularly (IVT; 200 and 400 μg/rat) induced a marked and dose-related increase in plasma PRL; EKNH2 (0.2 mg/kg, iv) induced a rise in plasma PRL similar to that evoked by Met-enk (400μg/rat). Metergoline (1 mg/kg, iv), a 5-HT receptor blocker, significantly reduced the PRL-releasing effect of Met-enk (200 μg/rat); these results were duplicated by using another 5-HT receptor blocker, i.e. methysergide (2.5 mg/kg, iv). Metergoline and methysergide also significantly reduced the increase in plasma PRL due to EKNH2. 5,6-Dihydroxytryptamine (50 μg, IVT), a neurotoxic drug which destroys 5-HT nerve terminals, almost completely...