Nitric oxide involvement in the anxiogenic-like effect of substance P

This study investigates whether nitric oxide (NO) is involved in the anxiogenic profile of action of substance P (SP) in mice in the elevated plus-maze (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. pretreatment) or 5 min later (i.c.v. pretreatment), the animals received i.c.v. injections of SP (10 pmol) or phosphate buffered saline (PBS) (2 microl). Afterwards, they were observed in the EPM. SP per se reduced the time spent on open arms, an anxiogenic-like effect. This effect was reverted by different NOS inhibitors and the NO donor. NOS inhibitors had no influence on the EPM parameters but the NO-releasing compound SNAP, as well as its parent thiol NAP, increased the animals' locomotor activity. 8-Br-cGMP (20 nmol), a permeable 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.