Improvement by repeated administration of 6R-tetrahydrobiopterin of 5,7-dihydroxytryptamine-induced abnormal behaviors in immature rats

• Published in: Biochemical and biophysical research communications Vol. 302; no. 1; pp. 156 - 161
• Main Authors: Mizuma, Hiroshi, Mizutani, Mika, Nozaki, Satoshi, Iizuka, Hirohito, Tohyama, Hideo, Nishimura, Nobuhiro, Watanabe, Yasuyoshi, Kohashi, Ryuichiro
• Format: Journal Article
• Language: English
• Published: United States 28-02-2003
• Subjects: 5,7-Dihydroxytryptamine - antagonists & inhibitors; 5,7-Dihydroxytryptamine - pharmacology; Animals; Behavior, Animal - drug effects; Biopterins - administration & dosage; Biopterins - analogs & derivatives; Biopterins - pharmacology; Female; Injections, Intraventricular; Locomotion - drug effects; Pregnancy; Rats; Rats, Wistar; Serotonin - metabolism
• ISSN: 0006-291X
• DOI: 10.1016/s0006-291x(03)00128-1

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).