Actions of orphanin FQ/nociceptin on rat ventral tegmental area neurons in vitro

Fang Zheng, David Grandy, Steven Johnson

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

1. Non-dopamine (putative GABAergic) neurons in the ventral tegmental area are in a position to influence mesolimbic functions by their inhibitory terminals that impinge locally on dopamine neurons and via their GABAergic efferents that innervate mesolimbic structures. In the present study we investigated responses of non-dopamine and dopamine neurons, recorded intracellularly in the rat midbrain slice, to orphanin FQ/nociceptin, the endogenous ligand for opioid receptor-like orphan receptors. 2. When recording in either non-dopamine or dopamine neurons, orphanin FQ/nociceptin reduced the frequency of spike firing and caused membrane hyperpolarization under current-clamp, or produced outward current under voltage-clamp. Such responses were concentration-dependent and reversed at -108 mV and -102 mV in non-dopamine and dopamine neurons, respectively. 3. Hyperpolarizations to orphanin FQ/nociceptin were not altered by tetrodotoxin or the opioid receptor antagonist naloxone, but were reduced by the opioid receptor-like orphan receptor antagonist [Phe1 1ΦCH 2-NH)Gly 2]NC(1-13)NH 2 (1 μM). 4. In dopamine neurons, orphanin FQ/nociceptin reduced the frequency of bicuculline- and tetrodotoxin-sensitive spontaneous inhibitory postsynaptic potentials, and reduced the amplitude of stimulus-evoked inhibitory postsynaptic potentials. 5. Taken together, the above data provide evidence that both non-dopamine and dopamine neurons are important substrates for orphanin FQ/nociceptin within the ventral tegmental area. Simultaneous inhibition of both non-dopamine and dopamine pathways by orphanin FQ/nociceptin may account for its influences on various ventral tegmental area-related functions.

Original languageEnglish (US)
Pages (from-to)1065-1071
Number of pages7
JournalBritish Journal of Pharmacology
Volume136
Issue number7
DOIs
StatePublished - 2002

Fingerprint

Ventral Tegmental Area
Dopaminergic Neurons
Neurons
Inhibitory Postsynaptic Potentials
Tetrodotoxin
Opioid Receptors
Miniature Postsynaptic Potentials
GABAergic Neurons
Bicuculline
Narcotic Antagonists
Naloxone
Mesencephalon
nociceptin
In Vitro Techniques
Dopamine
Ligands
Membranes

Keywords

  • GABAergic neurons
  • Inhibition and disinhibition
  • Inhibitory postsynaptic potential
  • Orphanin FQ/nociceptin
  • Ventral tegmental area

ASJC Scopus subject areas

  • Pharmacology

Cite this

Actions of orphanin FQ/nociceptin on rat ventral tegmental area neurons in vitro. / Zheng, Fang; Grandy, David; Johnson, Steven.

In: British Journal of Pharmacology, Vol. 136, No. 7, 2002, p. 1065-1071.

Research output: Contribution to journalArticle

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N2 - 1. Non-dopamine (putative GABAergic) neurons in the ventral tegmental area are in a position to influence mesolimbic functions by their inhibitory terminals that impinge locally on dopamine neurons and via their GABAergic efferents that innervate mesolimbic structures. In the present study we investigated responses of non-dopamine and dopamine neurons, recorded intracellularly in the rat midbrain slice, to orphanin FQ/nociceptin, the endogenous ligand for opioid receptor-like orphan receptors. 2. When recording in either non-dopamine or dopamine neurons, orphanin FQ/nociceptin reduced the frequency of spike firing and caused membrane hyperpolarization under current-clamp, or produced outward current under voltage-clamp. Such responses were concentration-dependent and reversed at -108 mV and -102 mV in non-dopamine and dopamine neurons, respectively. 3. Hyperpolarizations to orphanin FQ/nociceptin were not altered by tetrodotoxin or the opioid receptor antagonist naloxone, but were reduced by the opioid receptor-like orphan receptor antagonist [Phe1 1ΦCH 2-NH)Gly 2]NC(1-13)NH 2 (1 μM). 4. In dopamine neurons, orphanin FQ/nociceptin reduced the frequency of bicuculline- and tetrodotoxin-sensitive spontaneous inhibitory postsynaptic potentials, and reduced the amplitude of stimulus-evoked inhibitory postsynaptic potentials. 5. Taken together, the above data provide evidence that both non-dopamine and dopamine neurons are important substrates for orphanin FQ/nociceptin within the ventral tegmental area. Simultaneous inhibition of both non-dopamine and dopamine pathways by orphanin FQ/nociceptin may account for its influences on various ventral tegmental area-related functions.

AB - 1. Non-dopamine (putative GABAergic) neurons in the ventral tegmental area are in a position to influence mesolimbic functions by their inhibitory terminals that impinge locally on dopamine neurons and via their GABAergic efferents that innervate mesolimbic structures. In the present study we investigated responses of non-dopamine and dopamine neurons, recorded intracellularly in the rat midbrain slice, to orphanin FQ/nociceptin, the endogenous ligand for opioid receptor-like orphan receptors. 2. When recording in either non-dopamine or dopamine neurons, orphanin FQ/nociceptin reduced the frequency of spike firing and caused membrane hyperpolarization under current-clamp, or produced outward current under voltage-clamp. Such responses were concentration-dependent and reversed at -108 mV and -102 mV in non-dopamine and dopamine neurons, respectively. 3. Hyperpolarizations to orphanin FQ/nociceptin were not altered by tetrodotoxin or the opioid receptor antagonist naloxone, but were reduced by the opioid receptor-like orphan receptor antagonist [Phe1 1ΦCH 2-NH)Gly 2]NC(1-13)NH 2 (1 μM). 4. In dopamine neurons, orphanin FQ/nociceptin reduced the frequency of bicuculline- and tetrodotoxin-sensitive spontaneous inhibitory postsynaptic potentials, and reduced the amplitude of stimulus-evoked inhibitory postsynaptic potentials. 5. Taken together, the above data provide evidence that both non-dopamine and dopamine neurons are important substrates for orphanin FQ/nociceptin within the ventral tegmental area. Simultaneous inhibition of both non-dopamine and dopamine pathways by orphanin FQ/nociceptin may account for its influences on various ventral tegmental area-related functions.

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