Effects of ethanol on the levels of brain 6R-L-erythro-5, 6, 7, 8-tetrahydrobiopterin in the inbred strains of mice. DBA/2J, C3H/HeJ and C57BL/6J with different alcohol preferences.
6R-L-erythro-5, 6, 7, 8-tetrahydrobiopterin (6R-BH4) is a coenzyme for tyrosine, tryptophan and phenylalanine hydroxylases, the former two of which are the initial and the rate-limiting enzymes in the biosynthesis of the catecholamines and serotonin, respectively. The present study was designed to determine the changes in concentrations of 6R-BH4 in striatum and midbrain of the inbred strains of mice, DBA/2J, C3H/HeJ and C57BL/6J, with different genetically determined alcohol preferences, following the injection of ethanol (EtOH). The intraperitoneal administration of EtOH (0, 1, 2 and 4 g/kg) significantly and dose-dependently reduced the levels of striatal and midbrain 6R-BH4 in DBA/2J mice with the lowest alcohol preference, and EtOH (4 g/kg, i.p.) reduced the level of striatal 6R-BH4 in C3H/HeJ with medium alcohol preference. Following the administration of EtOH (4 g/kg, i.p.), brain 6R-BH4 levels in C57BL/6J mice with high alcohol preference were lowered compared with the control group, but the difference did not reach statistic significance. EtOH has a tendency to reduce the brain 6R-BH4 levels in mice with lower alcohol preference or higher sensitivity to EtOH. Based on these findings, it was proposed that differences in alcohol drinking behavior in the inbred strains of mice was influenced by brain 6R-BH4.
Yoshimoto
K
K
Department of Legal Medicine, Kyoto Prefectural University of Medicine, Japan.
Sorimachi
Y
Y
Li
Y J
YJ
Uemura
K
K
Yayama
K
K
Tani
J
J
Ueda
S
S
Komura
S
S
D000428:Alcohol Drinking / Q000235:genetics; D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism / Q000502:physiology; D001921:Brain / Q000201:enzymology*; D003067:Coenzymes / Q000378:metabolism* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA
D003067:Coenzymes; D001708:Biopterins; D000431:Ethanol; C003402:sapropterin