5-hydroxytryptamine (5-HT)2 receptor involvement in acute 5-HT-evoked scratching but not in allergic pruritus induced by dinitrofluorobenzene in rats

We investigated the role of serotonin (5-hydroxytryptamine; 5-HT)(2) and 5-HT3 receptor subtypes in acute itch-associated scratching behavior as well as in an allergic pruritus model in rats. Intradermal 5-HT evoked hind limb scratching directed toward the injection site in naive rats. Scratching behavior was significantly reduced by pretreatment with the 5-HT2 receptor antagonist ketanserin. Intradermal injection of alpha-methylserotonin, a 5-HT2 receptor agonist, also elicited scratching behavior in a dose-dependent manner, indicating that acute 5-HT-induced scratching is mediated via peripheral 5-HT2 receptors. To produce a model of allergic pruritus, skin was sensitized by topical application of 5% dinitrofluorobenzene (DNFB). One month later, repeated challenge of the skin with 0.2% DNFB at weekly intervals elicited scratching as part of the immediate allergic response. Scratching was not affected by ketanserin or by the 5-HT3 receptor antagonist ondansetron, indicating that neither 5-HT2 nor 5-HT3 receptors is involved in itch-associated scratching behavior caused by allergic skin dermatitis in rats.