1 Nocistatin (NST) antagonizes several actions of nociceptin/orphanin FQ (N/OFQ), but acts on distinct receptors. As N/OFQ exerts anxiolytic-like actions in various tests, its behavioural actions in the elevated plus-maze (EPM) test were compared with those of bovine NST. 2 Five minutes after i.c.v. treatment, mice were placed on the EPM for 5 min and entries into and time spent on open and closed arms were recorded alongside other parameters. 3 NST (0.1 ± 3 pmol) reduced percentages of entries into (control 39.6+3.1%, peak e ect at 1 pmol NST 8.5+2.9%) and time spent on open arms (control 30.8+2.3%, NST 2.7+1.5%). The C-terminal hexapeptide of NST (NST-C6; 0.01 ± 10 pmol) closely mimicked these actions of NST, with peak e ects at 0.1 pmol. 4 N/OFQ (1 ± 100 pmol) increased percentages of entries into (control 38.5+3.4%; peak e ect at 10 pmol N/OFQ 67.9+4.9%) and time spent on open arms (control 32.0+3.8%; N/OFQ 74.9+5.8%). Closed arm entries, an index of locomotor activity, were unchanged by all peptides. 5 E ects of NST or NST-C6, but not N/OFQ, were still detectable 15 min after injection. Behaviour of animals co-injected with NST (1 pmol) or NST-C6 (0.1 pmol) plus N/OFQ (10 pmol) was indistinguishable from that of controls. 6 These results reveal potent anxiogenic-like actions of NST and NST-C6, and con®rm the anxiolytic-like properties of N/OFQ. As NST and N/OFQ both derive from preproN/OF, anxiety may be modulated in opposing directions depending on how this precursor is processed.
Central injections of nocistatin or its C-terminal hexapeptide exert anxiogenic-like effect on behaviour of mice in the plus-maze test
CALO', Girolamo;GUERRINI, Remo;
2002
Abstract
1 Nocistatin (NST) antagonizes several actions of nociceptin/orphanin FQ (N/OFQ), but acts on distinct receptors. As N/OFQ exerts anxiolytic-like actions in various tests, its behavioural actions in the elevated plus-maze (EPM) test were compared with those of bovine NST. 2 Five minutes after i.c.v. treatment, mice were placed on the EPM for 5 min and entries into and time spent on open and closed arms were recorded alongside other parameters. 3 NST (0.1 ± 3 pmol) reduced percentages of entries into (control 39.6+3.1%, peak e ect at 1 pmol NST 8.5+2.9%) and time spent on open arms (control 30.8+2.3%, NST 2.7+1.5%). The C-terminal hexapeptide of NST (NST-C6; 0.01 ± 10 pmol) closely mimicked these actions of NST, with peak e ects at 0.1 pmol. 4 N/OFQ (1 ± 100 pmol) increased percentages of entries into (control 38.5+3.4%; peak e ect at 10 pmol N/OFQ 67.9+4.9%) and time spent on open arms (control 32.0+3.8%; N/OFQ 74.9+5.8%). Closed arm entries, an index of locomotor activity, were unchanged by all peptides. 5 E ects of NST or NST-C6, but not N/OFQ, were still detectable 15 min after injection. Behaviour of animals co-injected with NST (1 pmol) or NST-C6 (0.1 pmol) plus N/OFQ (10 pmol) was indistinguishable from that of controls. 6 These results reveal potent anxiogenic-like actions of NST and NST-C6, and con®rm the anxiolytic-like properties of N/OFQ. As NST and N/OFQ both derive from preproN/OF, anxiety may be modulated in opposing directions depending on how this precursor is processed.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
