RS-56812

The roles of serotonin (5-HT) and/or noradrenaline in acute pruriceptive processing have been demonstrated using antidepressants, such as milnacipran, a serotonin and noradrenaline reuptake inhibitor, and mirtazapine, a noradrenergic and specific serotonergic antidepressant; however, the involvement of 5-HT in acute pruriceptive processing has not yet been elucidated in detail. Scratching events induced by chloroquine (CQ) were attenuated by the administration of milnacipran or mirtazapine, and these effects were reversed by a treatment with ondansetron, a 5-HT₃ antagonist, or SB26970, a 5-HT₇ antagonist. CQ-induced scratching events were also ameliorated by the intrathecal administration of 5-HT, SR572227A and RS56812 (5-HT₃ agonists), and LP211 and LP44 (5-HT₇ agonists), indicating the modulation of CQ-induced scratching events by 5-HT and noradrenaline. By contrast, histamine-induced scratching events were not markedly affected by the administration of 5-HT and 5-HT₇ agonists, whereas 5-HT₃ agonists exerted attenuating effects. Similarly, they were not clearly reversed by the administration of the 5-HT₇ antagonist, unlike a 5-HT₃ antagonist. Therefore, 5-HT is involved in the attenuating effects of milnacipran and mirtazapine on CQ- and histamine-induced scratching events, and 5-HT₃ and 5-HT₇ receptors play different roles in pruriceptive processing induced by histamine or CQ.