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Antidepressant- and anxiolytic-like effects of nociceptin/orphanin FQ receptor ligands

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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 affective disorders. It has been reported that the activation of NOP receptors produces anxiolytic-like effects in rodents in a large series of behavioral assays, i.e., elevated plus maze, light-dark aversion, operant conflict, fear-potentiated startle, pup ultrasonic vocalizations, and hole board tests. In contrast, the blockade of N/OFQ signaling obtained with NOP-selective antagonists promotes antidepressant-like effects in the forced swimming and tail suspension tests. In these assays, N/OFQ is inactive per se, but reverses the antidepressant-like effects of NOP antagonists. NOP receptor knockout mice show an antidepressant-like phenotype, and NOP antagonists are inactive in these animals. Thus, the activation of the NOP receptor seems to evoke anxiolytic-like effects while its blockade antidepressant-like effects. This appears to be a rather unique behavioral profile since the activation or the blockade of a given neuropeptide receptor produces, in most of the cases, both antidepressant- and anxiolytic-like effects. This particular behavioral profile, the possible mechanisms of action, and the therapeutic potential of NOP receptor ligands for the treatment of depression and anxiety disorders are discussed in this review article.

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Acknowledgements

This work was financially supported by the University of Ferrara (60% grant to GC) and the European Community (Marie Curie Incoming International Fellowship, 509520 - MOODNOP, to ECG).

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  1. Department of Experimental and Clinical Medicine, Section of Pharmacology and Neuroscience Center, University of Ferrara, Via Fossato di Mortara 19, 44100, Ferrara, Italy

    Elaine C. Gavioli & Girolamo Calo’

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  1. Elaine C. Gavioli
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  2. Girolamo Calo’
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Correspondence to Elaine C. Gavioli.

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Gavioli, E.C., Calo’, G. Antidepressant- and anxiolytic-like effects of nociceptin/orphanin FQ receptor ligands. Naunyn Schmied Arch Pharmacol 372, 319–330 (2006). https://doi.org/10.1007/s00210-006-0035-8

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  • DOI: https://doi.org/10.1007/s00210-006-0035-8

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