title: GABA(A) signalling is involved in N/OFQ anxiolytic-like effects but not in nocistatin anxiogenic-like action as evaluated in the mouse elevated plus maze.
abstract: Nociceptin/orphanin FQ (N/OFQ) and nocistatin are two neuropeptides originated from the same precursor prepronociceptin/orphanin FQ (ppN/OFQ). N/OFQ is the endogenous ligand of the NOP receptor, while the target of action of nocistatin is still unknown. N/OFQ modulates various biological functions, including anxiety. Conversely, nocistatin either behaves as a functional N/OFQ antagonist or evokes per se effects opposite to those of N/OFQ. Here we investigated the interaction between the anxiolytic-like effects of N/OFQ and the anxiogenic-like action of nocistatin with those evoked by GABA(A) receptor ligands in the mouse elevated plus maze. The anxiogenic-like effects of the GABA(A) receptor antagonist pentylenetetrazol (20mg/kg; intraperitoneal, i.p.) were abolished by the co-treatment with N/OFQ (10pmol; intracerebroventricular, i.c.v.) while potentiated by the administration of nocistatin (0.01pmol; i.c.v.). The anxiolytic-like effects of the benzodiazepine receptor agonist diazepam (0.75mg/kg, i.p.) were reversed by nocistatin (0.1pmol; i.c.v.), whereas signs of sedation were observed when mice were co-treated with diazepam and N/OFQ (3pmol). Interesting enough, the i.p. treatment with flumazenil (1mg/kg) blocked the anxiolytic-like effects of N/OFQ (10pmol; i.c.v.), but not the anxiogenic effect elicited by nocistatin. Collectively, our findings suggest that the effects on anxiety elicited by pentylenetetrazol and diazepam can be counteracted or potentiated in the presence of N/OFQ and nocistatin. In addition, the effects on anxiety of N/OFQ, but not nocistatin, appear to be dependent on the benzodiazepine site of the GABA(A) receptor.
authors.affiliation: Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, Brazil.
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Gavioli
authors.forename: Filipe S
authors.initials: FS
authors.lastname: Duarte
authors.forename: Remo
authors.initials: R
authors.lastname: Guerrini
authors.forename: Girolamo
authors.initials: G
authors.lastname: Calo
authors.forename: Giles A
authors.initials: GA
authors.lastname: Rae
authors.forename: Thereza C
authors.initials: TC
authors.lastname: M De Lima
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D058785:GABA-A Receptor Agonists; D008024:Ligands; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051379:Mice; D018847:Opioid Peptides / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D000097629:Nociceptin
chemical_list: D014151:Anti-Anxiety Agents; D003975:Diazepam; D058785:GABA-A Receptor Agonists; D008024:Ligands; D018847:Opioid Peptides; D011963:Receptors, GABA-A; D014665:Vasodilator Agents; D000097629:Nociceptin; C111148:nocistatin