Blockade of nociceptin/orphanin FQ-NOP receptor signalling produces antidepressant-like effects: pharmacological and genetic evidences from the mouse forced swimming test
by
Gavioli EC, Marzola G, Guerrini R, Bertorelli R,
Zucchini S, De Lima TC, Rae GA, Salvadori S, Regoli D, Calo G.
Department of Experimental and Clinical Medicine, Section of Pharmacology and Neuroscience Centre, University of Ferrara, via Fossato di Mortara 19, 44100 Ferrara, Italy Department of Pharmaceutical Sciences and Biotechnology Centre, University of Ferrara, 44100 Ferrara, Italy Schering-Plough Research Institute, San Raffaele Science Park, 20132 Milan, Italy Department of Pharmacology, CCB, Universidade Federal de Santa Catarina, Florianopolis, Brazil.
Eur J Neurosci 2003 May;17(9):1987-1990


ABSTRACT

Nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the NOP receptor, regulates several central functions such as pain transmission, learning and memory, fear and anxiety and feeding and locomotor activity. It has been recently reported that NOP receptor antagonists induce antidepressant-like effects in the mouse forced swimming test (FST), i.e. reduce immobility time. This assay was used in the present study for further investigating the involvement of the NOP receptor in depression states. In male Swiss mice, intracerebroventricular injection (i.c.v) of the novel NOP receptor antagonist, UFP-101 (1-10 nmol) dose-dependently reduced the immobility time (control 192 +/- 14 s, UFP-101 91 +/- 15 s). The effect of 3 or 10 nmol UFP-101 was fully or partially reversed, respectively, by the coadministration of 1 nmol N/OFQ, which was inactive per se. NOP receptor knockout mice showed a reduced immobility time compared with their wild-type littermates (wild-type 215 +/- 10 s, knockout 143 +/- 12 s). Moreover, i.c.v. injected UFP-101 (10 nmol) significantly reduced immobility time in wild-type mice but not in NOP receptor knockout animals. In conclusion, these results, obtained using a combined pharmacological and genetic approach, indicate that blockade of the N/OFQ-NOP receptor signalling in the brain produces antidepressant-like effects in the mouse FST. These findings support the NOP receptor as a candidate target for the development of innovative antidepressant drugs.
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