This study investigates whether nitric oxide (NO) is involved in the anxiog
enic profile of action of substance P (SP) in mice in the elevated plus-maz
e (EPM). Adult Swiss mice were injected with NOS inhibitors such as L-NOARG
(20 nmol/kg) i.p., L-NAME (3 nmol per site), 7-NI (0.25 nmol per site) i.c
.v. or vehicle (NaCl 0.9% i.p. or PBS i.c.v.). About 30 min (i.p. pretreatm
ent) or 5 min later (i.c.v. pretreatment) the animals received i.c.v. injec
tions of SP (10 pmol) or phosphate buffered saline (PBS) (2 mul). Afterward
s, they were observed in the EPM. SP per se reduced the time spent on open
arms, an anxiogenic-like effect. This effect was revel ted by different NOS
inhibitors and the NO donor. NOS inhibitors had no influence on the EPM pa
rameters but the NO-releasing compound SNAP, as well as its parent thiol NA
P, increased the animals' locomotor activity. 8-Br-cGMP (20 nmol), a permea
ble cGMP analog, promoted an anxiogenic-like effect per se and enhanced the
SP effect on the EPM. Altogether, these results suggest a putative NO role
in the mediation of the anxiogenic-like effect of SP. (C) 2001 Elsevier Sc
ience B.V. All rights reserved.