Itch-associated response induced by intradermal serotonin through 5-HT2 receptors in mice

Serotonin (5-HT) is pruritogenic in humans and suggested to be involved in some pruritic diseases. Our experiments were carried out to determine wheth er an intradermal injection of 5-HT would elicit itch-associated response i n mice and to elucidate the 5-HT receptor subtypes involved in this 5-HT ac tion. 5-HT (14.1-235 nmol site(-1)) injected intradermally into the rostral back elicited scratching of the injected site, with bell-shaped dose-respo nse relationship. The scratching induced by 5-HT (100 nmol site(-1), peak e ffective dose) was suppressed by capsaicin (repeated administration) and th e opioid antagonist naloxone, features being similar to human itching. Scra tching was also elicited, by the 5-HT2 receptor agonist alpha-methylseroton in, but not by the 5-HT1A receptor agonist R(+)-8-hydroxy-N,N-dipropyl-2-am inotetralin nor the 5-HT3 receptor agonists 2-methylserotonin and 1- phenyl biganide, Scratching induced by 5-HT and alpha-methylserotonin was inhibite d by peroral pretreatment with 5-HT1/2 receptor antagonists methysergide an d cyproheptadine. 5-HT-induced scratching was also inhibited by intradermal injection of methysergide. Peroral pretreatment with 5-HT3 receptor antago nists ondansetron and 3-tropanyl-3, 5-dichrobenzoate did not significantly suppress 5-HT-induced scratching. The results suggest that scratching induc ed by intradermal injection of 5-HT is itch-associated response. The 5-HT a ction may be mediated at least partly by cutaneous 5-HT2 receptors. (C) 199 9 Elsevier Science Ireland Ltd. an rights reserved.