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.
Hirayama
Kenji
K
Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi, Fukuoka 812-8582, Japan.
Sudo
Nobuyuki
N
Sueyasu
Masanori
M
Sonoda
Junko
J
Chida
Youich
Y
Oishi
Ryozo
R
Kubo
Chiharu
C
D000315:Adrenalectomy; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000378:metabolism*; D006632:Histamine / Q000097:blood; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015735:Mifepristone / Q000008:administration & dosage / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D003189:p-Methoxy-N-methylphenethylamine / Q000008:administration & dosage / Q000494:pharmacology*
D005938:Glucocorticoids; D006727:Hormone Antagonists; D012333:RNA, Messenger; D015735:Mifepristone; D003189:p-Methoxy-N-methylphenethylamine; D006632:Histamine; D003346:Corticotropin-Releasing Hormone