Modulation of vestibular function by nociceptin/orphanin FQ: an in vivo and in vitro study

• Published in: Brain research Vol. 828; no. 1; pp. 74 - 82
• Main Authors: Sulaiman, M.Roslan, Niklasson, Magnus, Tham, Richard, Dutia, Mayank B.
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 15.05.1999; Amsterdam Elsevier; New York, NY
• Subjects: Action Potentials - drug effects; Animals; Biological and medical sciences; Calcium - pharmacology; Cobalt - pharmacology; Enkephalin, Leucine-2-Alanine - pharmacology; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Injections, Intraventricular; Medial vestibular nucleus; MEDICIN; MEDICINE; Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration; Neurons - drug effects; Neurons - physiology; Nociceptin; Opioid Peptides - pharmacology; Orphanin FQ; Peptide Fragments - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Opioid - agonists; Reflex, Vestibulo-Ocular - drug effects; Vertebrates: nervous system and sense organs; Vestibular Nuclei - cytology; Vestibular Nuclei - drug effects; Vestibulo-ocular reflex; Nociceptin; Orphanin FQ; Medial vestibular nucleus; Vestibulo-ocular reflex; Vertebrata; Mammalia; Rat; Vestibular nucleus; Rodentia; Central nervous system; Vestibular pathway; Vestibuloocular reflex; Brain (vertebrata)
• ISSN: 0006-8993; 1872-6240; 1872-6240
• DOI: 10.1016/S0006-8993(99)01331-1

The effects of nociceptin (orphanin FQ) on medial vestibular nucleus (MVN) neurons in vitro, and on vestibulo-ocular reflex (VOR) function in vivo, were investigated in order to determine the role of `opioid-like orphan' (ORL 1) receptors in modulating vestibular reflex function in the rat. Nociceptin (100 nM–1 μM) potently inhibited the spontaneous discharge of the majority (86%) of MVN neurons tested in the rat dorsal brainstem slice preparation in vitro. This inhibition was dose-dependent and persisted after blockade of synaptic transmission in low Ca 2+/Co 2+ medium. The inhibitory effects were insensitive to the opioid antagonist naloxone, but were effectively antagonised by the selective ORL 1 receptor antagonist, [Phe 1Ψ(CH 2–NH)Gly 2]Nociceptin(1–13)NH 2. The majority of MVN neurons (∼70%) were inhibited by both nociceptin and the δ-opioid receptor agonist, [ d-ala 2, d-leu 5]-enkephalin (DADLE), while a minority of cells (∼30%) were selectively responsive either to DADLE or to nociceptin, but not both. Co-application of nociceptin and DADLE to neurons that were responsive to both agonists, resulted in an inhibitory response that was the same as or less than the inhibition evoked by either agonist alone. Intracellular whole-cell patch clamp recordings from identified Type A and Type B MVN cells showed that both these cell types are responsive to nociceptin, which induced membrane hyperpolarisation and decrease in input resistance consistent with its known effects on membrane K currents in other cell types. In alert rats, i.c.v. injection of nociceptin caused a significant decrease in the gain of the hVOR and resulted in a prolongation of post-rotatory nystagmus in darkness. The decrease in VOR gain and the increase in the VOR time-constant was significant even at low doses of nociceptin which did not cause other observable behavioural effects. These findings demonstrate that endogenously released nociceptin may have a hitherto unexplored role in the functional modulation of the neural pathways that mediate vestibular reflexes in vivo.