The role played by brain serotonin (5-HT) neurotransmission in mediating the PRL-releasing effect on enkephalins was investigated in the rat. Both Met 5-enkephalin (Met-enk) and (D-Met 2, Pro)-enkephalinamide (EKNH 2), 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; EKNH 2 (0.2 mg/kg, iv) induced a rise in plasma PRL similar to that evoked by Met-enk (400 μg/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 EKNH 2. 5,6-Dihydroxytryptamine (50 μg, IVT), a neurotoxic drug which destroys 5-HT nerve terminals, almost completely abolished the rise in plasma PRL induced by the EKNH 2 (1.0 mg/kg, ip). However, blockade of 5-HT biosynthesis by p-chlorophenylalanine (100 mg/kg, sc, twice) potentiated the rise in plasma PRL induced by EKNH 2, an effect possibly resulting from the development of supersensitive 5-HT receptors. Pretreatment with quipazine (15 mg/kg, iv), a direct stimulant of 5-HT receptors, almost completely suppressed the PRL-releasing effect of Met-enk (400 μg/rat), EKNH 2, and IVT injected 5-HT (2 μg/rat). Blockade of catecholamine neurotransmission by α-methyl-p-tyrosine (200 mg/kg, ip) did not modify the PRL-releasing effect of EKNH 2. In all, these results suggest that enkephalins exert their PRL-releasing effect via mediation of the brain 5-HT system.
|Titolo:||Involvement of brain serotonin in the prolactin-releasing effect of opioid peptides|
|Parole Chiave:||Animals; Desipramine; Serotonin; Endorphins; Methysergide; Rats; Methyltyrosines; Prolactin; Quipazine; 5,6-Dihydroxytryptamine; Fenclonine; Metergoline; Synaptic Transmission; Enkephalins; Male|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||lug-1979|
|Digital Object Identifier (DOI):||10.1210/endo-105-1-163|
|Appare nelle tipologie:||01 - Articolo su periodico|