The Influence of hyperactivity of the hypothalamic-pituitary-adrenal axis and hyperglycemia on the 5-HT2A receptor-mediated wet-dog shake responses in rats.
Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis induces hyperglycemia and serotonin (5-HT)2A receptor supersensitivity. In the present study, to investigate the effect of hyperglycemia on the function of 5-HT2A receptors, we compared the 5-HT2A receptor-mediated wet-dog shake responses in rats treated with adrenocorticotropic hormone (ACTH), dexamethasone and streptozotocin. ACTH (100 ug/rat per day, s.c.), dexamethasone (1 mg/kg per day, s.c.) and streptozotocin (60 mg/kg, i.p.) produced significant hyperglycemia at 14 days after the start of these treatments, and the hyperglycemia was most pronounced in the streptozotocin-treated rats. The wet-dog shake responses induced by (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT2A receptor agonist, were significantly enhanced at 14 days after repeated treatment with ACTH and dexamethasone. However, streptozotocin-induced diabetes had no effect on the wet-dog shake responses. The results of the present study suggest that hyperglycemia is not strongly associated with the enhanced susceptibility of 5-HT2A receptors under the condition of hyperactivity of the HPA axis.
Umeda
Yuichi
Y
Department of Clinical Pharmacology and Pharmacy, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.
Amano
Manabu
M
Suemaru
Katsuya
K
Yamaguchi
Takumi
T
Kitamura
Yoshihisa
Y
Gomita
Yutaka
Y
Kawasaki
Hiromu
H
Araki
Hiroaki
H
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D005938:Glucocorticoids / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology; D006943:Hyperglycemia / Q000503:physiopathology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology; D013311:Streptozocin / Q000494:pharmacology
D005938:Glucocorticoids; D006728:Hormones; D044402:Receptor, Serotonin, 5-HT2A; D013311:Streptozocin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone