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Excessive grooming behaviour is induced by intracerebroventricular injections of the neuropeptide glutamic acid isoleucine amide (neuropeptide-EI), via the activation of A-10 dopaminergic neurons and the noradrenergic system. Our object was to study the latter system involved in these behaviours, using male Wistar rats weighing 250-300 g with i.c.v. implants. The results show that all the adrenoceptor antagonists "per se" do not affect excessive grooming behaviour or motor activity. Intracerebroventricular administration of propranolol, a general β-adrenoceptor antagonist, before neuropeptide-EI, inhibited the induced excessive grooming behaviour in a dose dependent manner. Metoprolol, a β1-adrenoceptor antagonist, also blocked this behaviour. However, intracerebroventricular injections of phentolamine, an α-adrenoceptor antagonist, and ((±)-1-[2,3-(Dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol), a β2-adrenoceptor antagonist, had no effect on the behaviour induced by neuropeptide-EI induced behaviour for any of the doses tested. On the other hand, isoproterenol, a general β-adrenoceptor agonist and dobutamine, a β1-adrenoceptor agonist, both elicited similar behaviours as those induced by neuropeptide-EI. These results support the hypothesis that a relationship exists between neuropeptide-EI and β-adrenoceptors, more specifically the β1-adrenoceptor, as found with other similar endogenous peptides such as neurotensin, cholecystin, substance P and α-melanocyte stimulating hormone. Hence, neuropeptide-EI could probably be exerting a neuromodulating effect on the central nervous system. © 2007 Elsevier B.V. All rights reserved. Fil: Sánchez Borzone, Mariela E.. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Cátedra de Bacteriología y Virología Médica. Laboratorio de Ciencias Fisiológicas; Argentina Fil: Attademo, Andres Maximiliano. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Cátedra de Bacteriología y Virología Médica. Laboratorio de Ciencias Fisiológicas; Argentina. Universidad Nacional del Litoral. Facultad de Humanidades y Ciencias. Laboratorio de Ecotoxicologia; Argentina Fil: Baiardi, Gustavo Carlos. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Cátedra de Bacteriología y Virología Médica. Laboratorio de Ciencias Fisiológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina Fil: Celis, María Ester. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Cátedra de Bacteriología y Virología Médica. Laboratorio de Ciencias Fisiológicas; Argentina

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.