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Circadian Variation in R‐THBP‐Induced Enhancement of the Ambulation‐Increasing Effect of Methamphetamine on Mice

Abstract: 6R‐L‐erythro‐5,6,7,8‐tetrahydrobiopterin (R‐THBP), a co‐factor for tyrosine hydroxylase and tryptophan hydroxylase, induces the enhancement of ambulation‐increasing effect of methamphetamine on mice. In this study, we investigated the circadian variation in the interaction between R‐THBP and methamphetamine by changing the time‐of‐day of both methamphetamine administration and pretreatment with R‐THBP. The mouse's ambulatory activity was measured by a tilting‐type activity cage for 4 hr. In the daytime, but not in the nighttime, the ambulation‐increasing effect of methamphetamine (1 and 2 mg/kg, s.c.) was significantly enhanced by the pretreatment with R‐THBP (100 mg/kg, s.c., 2 or 6 hr before). These data indicate the possibility that peripherally administered R‐THBP increases the biosynthesis of catecholamine especially in the daytime.