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Chronic treatment with the selective NOP receptor antagonist [Nphe1,Arg14,Lys15]N/OFQ-NH2 (UFP-101) reverses the behavioural and biochemical effects of unpredictable chronic mild stress in rats

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Abstract

Introduction

The present study was designed to assess the antidepressant effects of UFP-101, a selective nociceptin/orphanin FQ peptide (NOP) receptor antagonist, in a validated animal model of depression: the chronic mild stress (CMS).

Materials and methods and Results

UFP-101 (5, 10 and 20 nmol/rat; i.c.v., once a day for 21 days) dose- and time-dependently reinstated sucrose consumption in stressed animals without affecting the same parameter in non-stressed ones. In the forced swimming test, UFP-101 reduced immobility of stressed rats from day 8 of treatment. After a 3-week treatment, rats were killed for biochemical evaluations. UFP-101 abolished increase in serum corticosterone induced by CMS and reverted changes in central 5-HT/5-HIAA ratio. The behavioural and biochemical effects of UFP-101 mimicked those of imipramine, the reference antidepressant drug, administered at the dose of 15 mg/kg (i.p.). Co-administration of nociceptin/orphanin FQ (5 nmol/rat, from day 12 to 21) prevented the effects of UFP-101. Brain-derived neurotrophic factor mRNA and protein in hippocampus were not reduced by CMS nor did UFP-101 modify these parameters.

Discussion and Conclusion

This study demonstrated that chronic treatment with UFP-101 produces antidepressant-like effects in rats subjected to CMS supporting the proposal that NOP receptors represent a candidate target for the development of innovative antidepressant drugs.

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Acknowledgements

Funding for this study was provided the Italian Ministry of University (PRIN 2006 grant to M. Massi). We thank Prof. Elena Righi, expert in biomedical data analysis, for the precious assistance in data re-elaboration and Dr. Cristina Benatti, post-graduate technician in Neuroscience, for her help in SPSS data evaluation and revision. Mr Stefano Malaguti, who technically assisted with the execution of the experiments, and Miss Sonia Pennella, for her contribution in the final part of the organisation of the experiments prior to her degree thesis are also acknowledged.

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  1. Department of Biomedical Sciences, Section of Pharmacology, University of Modena and Reggio Emilia, 41100, Modena, Italy

    Giovanni Vitale, Valentina Ruggieri, Monica Filaferro, Claudio Frigeri, Silvia Alboni, Fabio Tascedda & Nicoletta Brunello

  2. Department of Pharmaceutical Sciences, and Biotechnology Center, University of Ferrara, 44100, Ferrara, Italy

    Remo Guerrini

  3. Department of Experimental Medicine and Public Health, University of Camerino, 62032, Camerino, Italy

    Carlo Cifani & Maurizio Massi

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  1. Giovanni Vitale
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Vitale, G., Ruggieri, V., Filaferro, M. et al. Chronic treatment with the selective NOP receptor antagonist [Nphe1,Arg14,Lys15]N/OFQ-NH2 (UFP-101) reverses the behavioural and biochemical effects of unpredictable chronic mild stress in rats. Psychopharmacology 207, 173–189 (2009). https://doi.org/10.1007/s00213-009-1646-9

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