Endogenous glucocorticoids inhibit scratching behavior induced by the administration of compound 48/80 in mice

In this study, we investigated the effects of endogenous glucocorticoids on the compound 48/80 (a condensation product of N-methyl-p-methoxyphenethylamine with formaldehyde)-induced mouse scratching behavior using either RU-486 (mifepristone), a glucocorticoid receptor antagonist, or a surgical resection of the adrenal glands. Subcutaneous injection of compound 48/80 induced not only a corticosterone elevation in the plasma but also an enhanced expression of corticotropin releasing hormone (CRH) mRNA in the paraventricular nucleus, which thus suggests that hypothalamic-pituitary-adrenal axis is activated by the compound 48/80-induced cutaneous reaction. Inhibition of such an endogenous glucocorticoid activity by RU-486 significantly increased the degree of scratching behavior at not only the early-phase (<60 min) but also the late-phase (>60 min) time course after the injection of compound 48/80. Since the elevation of the histamine levels in the plasma in the RU-486-treated mice was no longer found in late-phase scratching behavior, these results thus indicate that histamine is a dominant mediator responsible for early-phase scratching behavior, while different mediators other than histamine may be also involved in the induction of late-phase scratching behavior. Moreover, surgical removal of adrenal glands also significantly increased the compound 48/80-induced scratching behavior without affecting anxiety and locomotor parameters, indicating that endogenous glucocorticoids exert their anti-pururitogenic effects independently of changes in behavioral performance. In conclusion, endogenous glucocorticoid activity was found to suppress the compound 48/80-induced scratching behavior in mice.