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

Abstract

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.