Inhibitory effect of nociceptin on [3H]-5-HT release from rat cerebral cortex slices

1 The effect of nociceptin (NC) on S-hydroxytryptamine (5-HT) release was studied in rat cerebral cortex slices preincubated with [H-3]-5-HT and electrically stimulated (3 Hz for 2 min) at the 45th (St(1)) and the 75th (St(2)) min of superfusion. 2 NC (0.1-3 mu M), present in the medium from the 70th min onward, concentration-dependently reduced electrically evoked [H-3]-5-HT efflux (pEC(50) = 6.54, E-max -54%). The inhibition was not antagonized by naloxone (1 mu M) ruling out the involvement of opioid receptors. 3 Phe(1)psi(CH2-NH2)Gly(2)]NC(1-13)NH2, which acts as an opioid-like receptor (ORL1) antagonist at the peripheral level, behaved as a partial agonist in cerebral cortex slices i.e. it inhibited [H-3]-5-HT efflux when added before St(2), however, when present in the medium throughout the whole experiment, [Phe(1)psi(CH2-NH2)Gly(2)]NC(1-13)NH2 prevented the action of NC added at the 70th min. 4 The non-selective ORL1 receptor antagonist, naloxone benzoylhydrazone (3 mu M), in the presence of 10 mu M naloxone, did not modify the St(2)/St(1), ratio but completely abolished the NC effect. 5 These findings demonstrate that NC inhibits 5-HT release from rat cerebral cortex slices via ORL1, receptors, suggesting its involvement in central processes :mediated by 5-HT.