Inhibitory effect of nociceptin on [³H]-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 [³H]-5-HT and electrically stimulated (3 Hz, for 2 min) at the 45th (St₁) and the 75th (St₂) min of superfusion.

• NC (0.1–3 μM), present in the medium from the 70th min onward, concentration-dependently reduced electrically evoked [³H]-5-HT efflux (pEC₅₀=6.54, E_max −54%). The inhibition was not antagonized by naloxone (1 μM) ruling out the involvement of opioid receptors.

• Phe¹ψ(CH₂-NH₂)Gly²]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 [³H]-5-HT efflux when added before St₂, however, when present in the medium throughout the whole experiment, [Phe¹ψ(CH₂-NH₂)Gly²]NC(1-13)NH₂ prevented the action of NC added at the 70th min.

• The non-selective ORL₁ receptor antagonist, naloxone benzoylhydrazone (3 μM), in the presence of 10 μM naloxone, did not modify the St₂/St₁ ratio but completely abolished the NC effect.

• 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.

British Journal of Pharmacology (1999) 128, 119–123; doi:10.1038/sj.bjp.0702793