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NOP Ligands for the Treatment of Anxiety and Mood Disorders

  • Elaine C. Gavioli
  • Victor A. D. Holanda
  • Chiara Ruzza
Chapter
Part of the Handbook of Experimental Pharmacology book series

Abstract

Many studies point toward the nociceptin/orphanin FQ (N/OFQ) and the N/OFQ peptide receptor (NOP) as targets for the development of innovative drugs for treating anxiety- and mood-related disorders. Evidence supports the view that the activation of NOP receptors with agonists elicits anxiolytic-like effects, while its blockade with NOP antagonists promotes antidepressant-like actions in rodents. Genetic studies showed that NOP receptor knockout mice display an antidepressant-like phenotype, and NOP antagonists are inactive in these animals. In contrast, the genetic blockade of NOP receptor signaling generally displays an increase of anxiety states in the elevated plus-maze test. In this chapter we summarized the most relevant findings of NOP receptor ligands in the modulation of anxiety and mood disorders, and the putative mechanisms of action are discussed.

Keywords

Animal behavior Anxiety Depression Nociceptin/orphanin FQ NOP receptor Stress 

Abbreviations

ACTH

Adrenocorticotropic hormone

BDNF

Brain-derived neurotrophic factor

BNST

Bed nucleus of the stria terminalis

CRF

Corticotropin-releasing factor

DRL

Differential reinforcement of low rate schedule

DRN

Dorsal raphe nucleus

FGF-2

Fibroblast growth factor

HPA

Hypothalamus-pituitary-adrenal axis

Icv

Intracerebroventricular

IL-6

Interleukin-6

J-113397

1-[(3R,4R)-1-(cyclooctylmethyl)-3-(hydroxymethyl)-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one

JTC-801

N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl)benzamide hydrochloride

LPS

Bacterial lipopolysaccharide

LY2940094

[2-[4-[(2-chloro-4,4-difluoro-spiro[5Hthieno[2,3-c]pyran-7,4′-piperidine]-1′-yl)methyl]-3-methylpyrazol-1-yl]-3-pyridyl]methanol

N/OFQ

Nociceptin/orphanin FQ

NOP(−/−)

Mice knockout for the NOP receptor

ppN/OFQ

N/OFQ precursor

ppN/OFQ(−/−)

Mice knockout for the N/OFQ precursor

PTSD

Post-traumatic stress disorder

PVN

Paraventricular nucleus of hypothalamus

Ro 64-6198

(1S,3aS)-8-(2,3,3a,4,5,6-Hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one

Ro 65-6570

(RS)-8-(1,2-Dihydro-1-acenaphthylenyl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one

SB-612111

(5S,7S)-7-[[4-(2,6-dichlorophenyl)-1-piperidinyl]methyl]-6,7,8,9-tetrahydro-1-methyl-5H-benzocyclohepten-5-ol

SNP

Single-nucleotide polymorphism

SSRI

Selective serotonin reuptake inhibitor

TNF-α

Tumor necrosis factor-α

UFP-101

[Nphe1, Arg14, Lys15] N/OFQ-NH2

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Elaine C. Gavioli
    • 1
  • Victor A. D. Holanda
    • 1
  • Chiara Ruzza
    • 2
  1. 1.Behavioral Pharmacology Laboratory, Department of Biophysics and PharmacologyFederal University of Rio Grande do NorteNatalBrazil
  2. 2.Department of Medical Sciences, Section of Pharmacology, and National Institute of NeuroscienceUniversity of FerraraFerraraItaly

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