The nociceptin receptor-mediated inhibition of the rat rostral ventrolateral medulla neurons in vitro

The recently available antagonist selective for novel nociceptin receptor, [Phe(1)psi(CH2-NH)Gly(2)]NC(1-13)NH2, was utilized in this study to verify specificity of nociceptin receptor in mediating the nociceptin-induced inhibition of electrical activity of neurons in the rostral ventrolateral medulla of rat brain slices. Perfusion of nociceptin (10 nM) considerably reduced spontaneously firing frequency of the medullary neurons. Co-perfusion of [Phe(1)psi(CH2-NH)Gly(2)]NC(1-13)NH2 (10 mu M) completely blocked the nociceptin-induced depression of the neuronal activity. Blocking effect of [Phe(1)psi(CH2-NH)Gly(2)]NC(1-13)NH2 was concentration-dependent. However, the nociceptin antagonist did not modify basal, and opioid peptide enkephalin-depressed, firing rates of the neurons. In contrast to [Phe(1)psi(CH2-NH)Gly(2)]NC(1-13)NH2, the non-selective opioid receptor antagonist naloxone (10 mu M) failed to affect the nociceptin inhibition even though naloxone at a lower concentration (1 mu M) readily blocked enkephalin-induced depression of the neuronal activity. These data indicate that the nociceptin-induced inhibition of spontaneous discharge of the rostral ventrolateral medulla neurons is specifically mediated by [Phe(1)psi(CH2-NH)Gly(2)]NC(1-13)NH2-sensitive nociceptin receptors distinct from typical naloxone-sensitive opioid receptors. (C) 1999 Elsevier Science B.V. All rights reserved.