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Antidepressant-like effects of the nociceptin/orphanin FQ receptor antagonist UFP-101: new evidence from rats and mice.
Naunyn Schmiedebergs Arch Pharmacol. 2004 Jun; 369(6):547-53.NS

Abstract

Receptor antagonist and knockout studies have demonstrated that blockade of signalling via nociceptin/orphanin FQ (N/OFQ) and its receptor (NOP) has antidepressant-like effects in mice submitted to the forced swimming test (FST). The aim of the present study was to explore further the antidepressant-like properties of the NOP antagonist UFP-101 in different species (mouse and rat) and using different assays [FST and tail suspension test (TST)], and to investigate the mechanism(s) involved in its actions.UFP-101 (10 nmol i.c.v.) reduced immobility time of Swiss mice in the TST (mean+/-SEM) from 179+/-11 to 111+/-10 s. N/OFQ (1 nmol i.c.v.) was without effect per se, but fully prevented the effect of UFP-101. The spontaneous immobility time of NOP(-/-) CD1-C57BL/6J-129 mice in the TST was much lower than that of wild-type (NOP(+/+)) littermates (75+/-11 vs. 144+/-17 s) or of Swiss mice. UFP-101 (10 nmol i.c.v.) decreased immobility time (-65%) and increased climbing time (71%) in rats submitted to the FST. In rat brain slices, N/OFQ (100 nM) triggered robust K(+)-dependent hyperpolarizing currents in locus coeruleus and dorsal raphe neurons. UFP-101 (3 microM) fully prevented N/OFQ-induced currents, but was inactive per se. Fluoxetine, desipramine (both 30 mg/kg i.p.) and UFP-101 (10 nmol i.c.v.) reduced immobility time of mice in the FST. The serotonin synthesis inhibitor p-chlorophenylalanine methylester (PCPA, 4 x 100 mg/kg per day i.p.) prevented the antidepressant-like effects of fluoxetine and UFP-101 (but not desipramine), whereas N-(2-chloroethyl)- N-ethyl-2-bromobenzylamine (DSP-4, neurotoxic for noradrenergic neurons; 50 mg/kg i.p., 7 days beforehand), suppressed only the effect of desipramine. Neither pretreatment affected spontaneous immobility time per se.Thus, UFP-101 exhibits pronounced antidepressant-like effects in different species and animal models, possibly by preventing the inhibitory effects of endogenous N/OFQ on brain monoaminergic (in particular serotonergic) neurotransmission. Participation of the N/OFQ-NOP receptor system in mood modulation sets new potential targets for antidepressant drug development.

Authors+Show Affiliations

Department of Experimental and Clinical Medicine, Section of Pharmacology and Neuroscience Center, University of Ferrara, via Fossato di Mortara 19, 44100 Ferrara, Italy.No 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 availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15197534

Citation

Gavioli, E C., et al. "Antidepressant-like Effects of the Nociceptin/orphanin FQ Receptor Antagonist UFP-101: New Evidence From Rats and Mice." Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 369, no. 6, 2004, pp. 547-53.
Gavioli EC, Vaughan CW, Marzola G, et al. Antidepressant-like effects of the nociceptin/orphanin FQ receptor antagonist UFP-101: new evidence from rats and mice. Naunyn Schmiedebergs Arch Pharmacol. 2004;369(6):547-53.
Gavioli, E. C., Vaughan, C. W., Marzola, G., Guerrini, R., Mitchell, V. A., Zucchini, S., De Lima, T. C., Rae, G. A., Salvadori, S., Regoli, D., & Calo', G. (2004). Antidepressant-like effects of the nociceptin/orphanin FQ receptor antagonist UFP-101: new evidence from rats and mice. Naunyn-Schmiedeberg's Archives of Pharmacology, 369(6), 547-53.
Gavioli EC, et al. Antidepressant-like Effects of the Nociceptin/orphanin FQ Receptor Antagonist UFP-101: New Evidence From Rats and Mice. Naunyn Schmiedebergs Arch Pharmacol. 2004;369(6):547-53. PubMed PMID: 15197534.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antidepressant-like effects of the nociceptin/orphanin FQ receptor antagonist UFP-101: new evidence from rats and mice. AU - Gavioli,E C, AU - Vaughan,C W, AU - Marzola,G, AU - Guerrini,R, AU - Mitchell,V A, AU - Zucchini,S, AU - De Lima,T C M, AU - Rae,G A, AU - Salvadori,S, AU - Regoli,D, AU - Calo',G, Y1 - 2004/05/25/ PY - 2003/10/02/received PY - 2004/04/16/accepted PY - 2004/6/16/pubmed PY - 2005/2/23/medline PY - 2004/6/16/entrez SP - 547 EP - 53 JF - Naunyn-Schmiedeberg's archives of pharmacology JO - Naunyn Schmiedebergs Arch. Pharmacol. VL - 369 IS - 6 N2 - Receptor antagonist and knockout studies have demonstrated that blockade of signalling via nociceptin/orphanin FQ (N/OFQ) and its receptor (NOP) has antidepressant-like effects in mice submitted to the forced swimming test (FST). The aim of the present study was to explore further the antidepressant-like properties of the NOP antagonist UFP-101 in different species (mouse and rat) and using different assays [FST and tail suspension test (TST)], and to investigate the mechanism(s) involved in its actions.UFP-101 (10 nmol i.c.v.) reduced immobility time of Swiss mice in the TST (mean+/-SEM) from 179+/-11 to 111+/-10 s. N/OFQ (1 nmol i.c.v.) was without effect per se, but fully prevented the effect of UFP-101. The spontaneous immobility time of NOP(-/-) CD1-C57BL/6J-129 mice in the TST was much lower than that of wild-type (NOP(+/+)) littermates (75+/-11 vs. 144+/-17 s) or of Swiss mice. UFP-101 (10 nmol i.c.v.) decreased immobility time (-65%) and increased climbing time (71%) in rats submitted to the FST. In rat brain slices, N/OFQ (100 nM) triggered robust K(+)-dependent hyperpolarizing currents in locus coeruleus and dorsal raphe neurons. UFP-101 (3 microM) fully prevented N/OFQ-induced currents, but was inactive per se. Fluoxetine, desipramine (both 30 mg/kg i.p.) and UFP-101 (10 nmol i.c.v.) reduced immobility time of mice in the FST. The serotonin synthesis inhibitor p-chlorophenylalanine methylester (PCPA, 4 x 100 mg/kg per day i.p.) prevented the antidepressant-like effects of fluoxetine and UFP-101 (but not desipramine), whereas N-(2-chloroethyl)- N-ethyl-2-bromobenzylamine (DSP-4, neurotoxic for noradrenergic neurons; 50 mg/kg i.p., 7 days beforehand), suppressed only the effect of desipramine. Neither pretreatment affected spontaneous immobility time per se.Thus, UFP-101 exhibits pronounced antidepressant-like effects in different species and animal models, possibly by preventing the inhibitory effects of endogenous N/OFQ on brain monoaminergic (in particular serotonergic) neurotransmission. Participation of the N/OFQ-NOP receptor system in mood modulation sets new potential targets for antidepressant drug development. SN - 0028-1298 UR - https://www.unboundmedicine.com/medline/citation/15197534/Antidepressant_like_effects_of_the_nociceptin/orphanin_FQ_receptor_antagonist_UFP_101:_new_evidence_from_rats_and_mice_ L2 - https://dx.doi.org/10.1007/s00210-004-0939-0 DB - PRIME DP - Unbound Medicine ER -