Improvement by repeated administration of 6R-tetrahydrobiopterin of 5,7-dihydroxytryptamine-induced abnormal behaviors in immature rats.
To clarify the therapeutic effects of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH(4)) on the abnormal behaviors induced by neonatal 5,7-dihydroxytryptamine (5,7-DHT, 100 microg; i.c.v.) treatment in immature rats, 6R-BH(4) (10-40 mg/kg) was administered intraperitoneally from 22nd to 28th days or only once on the 28th day. The locomotion activities decreased dramatically in 5,7-DHT-treated rats (p<0.01; as compared to controls) on the 28th day. The reduced locomotion was recovered dose-dependently by repeated administration of 6R-BH(4), whereas it was not altered after a single injection of 6R-BH(4). In addition, repeated administration of 6R-BH(4) significantly facilitated 5-HT turnover ratio (5-HIAA/5-HT) in the striatum, cerebral cortex, and cerebellum. These findings suggest that the behavioral restoration by 6R-BH(4) might be due to the enhancement of 5-HT turnover by accumulated but not a single dose of 6R-BH(4).
Mizuma
Hiroshi
H
Depatment of Clinical Pathology, Kyorin University School of Health Sciences, 476 Miyashita-cho, Hachioji, Tokyo 192-8508, Japan.
Mizutani
Mika
M
Nozaki
Satoshi
S
Iizuka
Hirohito
H
Tohyama
Hideo
H
Nishimura
Nobuhiro
N
Watanabe
Yasuyoshi
Y
Kohashi
Ryuichiro
R
D015116:5,7-Dihydroxytryptamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001708:Biopterins / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005260:Female; D007276:Injections, Intraventricular; D008124:Locomotion / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism
D001708:Biopterins; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; C003402:sapropterin