NOP Ligands for the Treatment of Anxiety and Mood Disorders

  • Elaine C. GavioliEmail author
  • Victor A. D. Holanda
  • Chiara Ruzza
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 254)


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.


Animal behavior Anxiety Depression Nociceptin/orphanin FQ NOP receptor Stress 



Adrenocorticotropic hormone


Brain-derived neurotrophic factor


Bed nucleus of the stria terminalis


Corticotropin-releasing factor


Differential reinforcement of low rate schedule


Dorsal raphe nucleus


Fibroblast growth factor


Hypothalamus-pituitary-adrenal axis








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


Bacterial lipopolysaccharide




Nociceptin/orphanin FQ


Mice knockout for the NOP receptor


N/OFQ precursor


Mice knockout for the N/OFQ precursor


Post-traumatic stress disorder


Paraventricular nucleus of hypothalamus

Ro 64-6198


Ro 65-6570





Single-nucleotide polymorphism


Selective serotonin reuptake inhibitor


Tumor necrosis factor-α


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


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Elaine C. Gavioli
    • 1
    Email author
  • 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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