Involvement of nitric oxide in serotonin-induced scratching in mice.

Serotonin is a pruritogenic substance in humans and animals, but the mechanisms of action through which serotonin induces itch response are not yet understood. To examine the possible role of nitric oxide (NO) in the profile of scratching behaviour due to intradermal injection of serotonin in mice. Intradermal injection of serotonin (14.1-235 nmol per site) into the nape of the neck was used to elicit itch in mice. Scratching behaviour was evaluated by counting the number of bouts during 60 min after injection. To determine the possible involvement of the nitrergic system in serotonin-induced scratching, L-NG-nitroarginine methyl ester [L-NAME; a nonselective nitric oxide synthase (NOS) inhibitor], aminoguanidine [a selective inducible (i)NOS inhibitor] and L-arginine (an NO precursor) were administered intraperitoneally to control and serotonin-injected animals. Intradermal serotonin caused scratching in mice with a bell-shaped dose-response correlation, and the peak effective dose was 141 nmol per site. The majority of scratching bouts in animals occurred 5-10 min after injection. Ineffective doses of L-NAME (3 mg/kg IP) and aminoguanidine (100 mg/kg IP) decreased the scratching induced by intradermal serotonin injection in animals (P < 0.001 and P < 0.001), while an subeffective dose of L-arginine (100 mg/kg IP) augmented the scratching effect of serotonin (P < 0.001). We show for the first time that the scratching induced by intradermal serotonin is mediated by NOS, especially iNOS, activation. We conclude that NO may play a role in mediating itch responses. NO and NOS could be new targets for antipruritic agents.