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

The effect of nociceptin (NC) on 5‐hydroxytryptamine (5‐HT) release was studied in rat cerebral cortex slices preincubated with [ 3 H]‐5‐HT and electrically stimulated (3 Hz, for 2 min) at the 45th (St 1 ) and the 75th (St 2 ) min of superfusion. NC (0.1–3 μ M ), present in the medium from the 70th min onward, concentration‐dependently reduced electrically evoked [ 3 H]‐5‐HT efflux (pEC 50 =6.54, E max −54%). The inhibition was not antagonized by naloxone (1 μ M ) ruling out the involvement of opioid receptors. Phe 1 ψ(CH 2 ‐NH 2 )Gly 2 ]NC(1‐13)NH 2 , which acts as an opioid‐like receptor (ORL 1 ) antagonist at the peripheral level, behaved as a partial agonist in cerebral cortex slices i.e. it inhibited [ 3 H]‐5‐HT efflux when added before St 2 , however, when present in the medium throughout the whole experiment, [Phe 1 ψ(CH 2 ‐NH 2 )Gly 2 ]NC(1‐13)NH 2 prevented the action of NC added at the 70th min. The non‐selective ORL 1 receptor antagonist, naloxone benzoylhydrazone (3 μ M ), in the presence of 10 μ M naloxone, did not modify the St 2 /St 1 ratio but completely abolished the NC effect. These findings demonstrate that NC inhibits 5‐HT release from rat cerebral cortex slices via ORL 1 receptors, suggesting its involvement in central processes mediated by 5‐HT.British Journal of Pharmacology (1999) 128 , 119–123; doi: 10.1038/sj.bjp.0702793