Enhancement of ambulation-increasing effect of methamphetamine by peripherally-administered 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-THBP) in mice.
Behavioral effects of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-THBP), a co-factor for tyrosine hydroxylase and tryptophan hydroxylase, were investigated by means of ambulatory activity in mice. Single administration of R-THBP (50 and 100 mg/kg, s.c.) showed no significant effect on the mouse's ambulatory activity for 5 hr. The ambulation-increasing effect of methamphetamine (2 mg/kg, s.c.) was dramatically enhanced and prolonged by the pretreatment with R-THBP (100 mg/kg, s.c.) 0, 2, 6, 12 and 24 hr before, but not 18 or 36 hr before, the methamphetamine administration. However, when combined administration of R-THBP (100 mg/kg, s.c., 2 hr before) with methamphetamine (2 mg/kg, s.c.) was repeated at intervals of 3-4 days, the enhancement by R-THBP of the methamphetamine effect was observed only in the 1st and 2nd administration, but not in the later administration. The pretreatment with R-THBP (100 mg/kg, s.c., 2 hr before) enhanced the ambulation-increasing effect of ephedrine (80 mg/kg, i.p.), but failed to modify those of cocaine (20 mg/kg, s.c.), mazindol (2.5 mg/kg, s.c.), bromocriptine (8 mg/kg, i.p.), morphine (20 mg/kg, s.c.) and scopolamine (0.5 mg/kg, s.c.). It is noteworthy that R-THBP differentially modifies the ambulation-increasing effect of the above-mentioned drugs.
Department of Neuropsychiatry, Gunma University School of Medicine, Maebashi, Japan.
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D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D001971:Bromocriptine / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D004357:Drug Synergism; D004809:Ephedrine / Q000494:pharmacology; D008297:Male; D008454:Mazindol / Q000494:pharmacology; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D012601:Scopolamine / Q000494:pharmacology; D013997:Time Factors
D001708:Biopterins; D001971:Bromocriptine; D008694:Methamphetamine; D009020:Morphine; D008454:Mazindol; D012601:Scopolamine; C003402:sapropterin; D004809:Ephedrine; D003042:Cocaine