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 inhi bition of electrical activity of neurons in the rostral ventrolateral medul la of rat brain slices. Perfusion of nociceptin (10 nM) considerably reduce d 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 nocic eptin-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 n ociceptin antagonist did not modify basal, and opioid peptide enkephalin-de pressed, 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 m u M) failed to affect the nociceptin inhibition even though naloxone at a l ower concentration (1 mu M) readily blocked enkephalin-induced depression o f the neuronal activity. These data indicate that the nociceptin-induced in hibition of spontaneous discharge of the rostral ventrolateral medulla neur ons is specifically mediated by [Phe(1)psi(CH2-NH)Gly(2)]NC(1-13)NH2-sensit ive nociceptin receptors distinct from typical naloxone-sensitive opioid re ceptors. (C) 1999 Elsevier Science B.V. All rights reserved.