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Chronic treatment with the selective NOP receptor antagonist [Nphe 1, Arg 14, Lys 15]N/OFQ-NH 2 (UFP-101) reverses the behavioural and biochemical effects of unpredictable chronic mild stress in rats.
Psychopharmacology (Berl). 2009 Dec; 207(2):173-89.P

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.

Authors+Show Affiliations

Department of Biomedical Sciences, Section of Pharmacology, University of Modena and Reggio Emilia, 41100, Modena, Italy. giovanni.vitale@unimore.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19711054

Citation

Vitale, Giovanni, et al. "Chronic Treatment With the Selective NOP Receptor Antagonist [Nphe 1, Arg 14, Lys 15]N/OFQ-NH 2 (UFP-101) Reverses the Behavioural and Biochemical Effects of Unpredictable Chronic Mild Stress in Rats." Psychopharmacology, vol. 207, no. 2, 2009, pp. 173-89.
Vitale G, Ruggieri V, Filaferro M, et al. Chronic treatment with the selective NOP receptor antagonist [Nphe 1, Arg 14, Lys 15]N/OFQ-NH 2 (UFP-101) reverses the behavioural and biochemical effects of unpredictable chronic mild stress in rats. Psychopharmacology (Berl). 2009;207(2):173-89.
Vitale, G., Ruggieri, V., Filaferro, M., Frigeri, C., Alboni, S., Tascedda, F., Brunello, N., Guerrini, R., Cifani, C., & Massi, M. (2009). Chronic treatment with the selective NOP receptor antagonist [Nphe 1, Arg 14, Lys 15]N/OFQ-NH 2 (UFP-101) reverses the behavioural and biochemical effects of unpredictable chronic mild stress in rats. Psychopharmacology, 207(2), 173-89. https://doi.org/10.1007/s00213-009-1646-9
Vitale G, et al. Chronic Treatment With the Selective NOP Receptor Antagonist [Nphe 1, Arg 14, Lys 15]N/OFQ-NH 2 (UFP-101) Reverses the Behavioural and Biochemical Effects of Unpredictable Chronic Mild Stress in Rats. Psychopharmacology (Berl). 2009;207(2):173-89. PubMed PMID: 19711054.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chronic treatment with the selective NOP receptor antagonist [Nphe 1, Arg 14, Lys 15]N/OFQ-NH 2 (UFP-101) reverses the behavioural and biochemical effects of unpredictable chronic mild stress in rats. AU - Vitale,Giovanni, AU - Ruggieri,Valentina, AU - Filaferro,Monica, AU - Frigeri,Claudio, AU - Alboni,Silvia, AU - Tascedda,Fabio, AU - Brunello,Nicoletta, AU - Guerrini,Remo, AU - Cifani,Carlo, AU - Massi,Maurizio, Y1 - 2009/08/27/ PY - 2009/01/08/received PY - 2009/08/10/accepted PY - 2009/8/28/entrez PY - 2009/8/28/pubmed PY - 2010/4/9/medline SP - 173 EP - 89 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 207 IS - 2 N2 - 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. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/19711054/Chronic_treatment_with_the_selective_NOP_receptor_antagonist_[Nphe_1_Arg_14_Lys_15]N/OFQ_NH_2__UFP_101__reverses_the_behavioural_and_biochemical_effects_of_unpredictable_chronic_mild_stress_in_rats_ L2 - https://dx.doi.org/10.1007/s00213-009-1646-9 DB - PRIME DP - Unbound Medicine ER -