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 \ub1 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 \ub1 10 pmol) closely mimicked these actions of NST,
with peak e ects at 0.1 pmol.
4 N/OFQ (1 \ub1 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\uaerm 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