The effects of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin on ethanol-induced sleep time and ethanol elimination in inbred strains of mice with different alcohol preference.
6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4) is a coenzyme for tyrosine, tryptophan and phenylalanine hydroxylases. Male C57BL/6J and DBA/2J mice were given 6R-BH4 (0, 12.5, 25.0 and 50.0 mg/kg of body weight, i.v.) or saline, and then 4 h later, all animals were injected with ethanol (EtOH) (4.0 g/kg, i.p.), which causes them to lose the righting reflex, to investigate the differences in EtOH-induced sleeping time. 6R-BH4 pretreatment reduced EtOH-induced sleep time in DBA/2J mice with lower alcohol preference (p < 0.05), which showed no changes in the pharmacokinetics of blood EtOH. No changes in EtOH-induced sleep time were observed in C57BL/6J mice with higher alcohol preference. These results indicate that the sensitivity to EtOH in mice with lower alcohol preference was associated with 6R-BH4 activity in the CNS.
Yoshimoto
K
K
Department of Legal Medicine, Prefectural University of Medicine, Kyoto, Japan.
Yoshida
T
T
Takeuchi
Y
Y
Ueda
S
S
D000428:Alcohol Drinking / Q000523:psychology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000431:Ethanol / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D012890:Sleep / Q000187:drug effects*; D013997:Time Factors
D000975:Antioxidants; D002492:Central Nervous System Depressants; D001708:Biopterins; D000431:Ethanol; C003402:sapropterin