Distribution of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin in regional brain areas of inbred strains of rats and mice 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 catecholamines and serotonin, respectively. The present study was conducted to determine the levels of 6R-BH4 in the inbred strains of rats BN and F344, and the inbred strains of mice C57BL/6J, C3H/HeJ and DBA/2J, with different genetically determined alcohol preferences. Previous studies have shown that BN and F344 rats exhibit a high and low alcohol preference, respectively; that C57BL/6J and DBA/2J mice show a high and low alcohol preference, respectively, and that C3H/HeJ mice exhibit a moderate alcohol preference. The levels of 6R-BH4 were measured in five regional brain areas of rats and in two regional brain areas of mice. There was about a 3-fold difference in 6R-BH4 levels across the rat brain areas assayed, ranging from a low level in the frontal cortex to a high level in the striatum and midbrain. Midbrain 6R-BH4 levels in F344 rats were higher than those of BN rats (p < 0.05). On the other hand, striatal 6R-BH4 levels in DBA/2J mice were higher than those of the other two strains of mice (p < 0.05). These results indicate that 6R-BH4 is distributed throughout the nigro- and mesostriatal dopaminergic nervous systems, and that brain 6R-BH4 levels may be involved in the genetic differences in alcohol-drinking behavior in animal models.
Yoshimoto
K
K
Department of Legal Medicine, Kyoto Prefectural University of Medicine, Japan.
Komura
S
S
Uemura
K
K
Yayama
K
K
Ogata
M
M
Yoshida
T
T
Kozaki
N
N
D000428:Alcohol Drinking; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D000975:Antioxidants; D001708:Biopterins; C003402:sapropterin