論文摘要:
BH4(tetraphydrobiopterin)為合成腦中重要神經化學傳遍物質:多巴胺(depamine)等醇素的輔酶。在老鼠紋狀體中，其濃度在白晝時高，夜晚時低，和老鼠活動量成相反關係。藥理實驗發現:注射安非他命(amphetamin)興奮劑，會增加老鼠活動量，降低紋狀體濃度。臨床研究額示:服用適量安非他命，會使人數產生類似精神病現象，為Amphetarnin Psychoses，但對此疾病生理機轉不甚清楚。
本研究目的，在探討老鼠在短期、長期(持續與斷續)的安非他命作用下，在白晝和黑暗中是否會對BH4濃度、活動量造成週期(circadian rhymn )改變影響。
實驗一至三中，老鼠皆隨機分成實驗組(注射安非他命)和控制組(注射生理食鹽水)，且均在平均隨機抽取至四時區(6時、12時、18時、24時)施測。實驗一:兩組皆利用皮下滲透器連續平穩滲入體內6天後施測。實驗二:控制組和實驗組在各時區前1小時注射。實驗三:兩組都每隔4小時注射，為期6天後施測。所有實驗老鼠均於測完行為後立即犧牲取腦，取紋狀體進行化學分析。
實驗結果為(1)短期與長期性的安非他命作用，均會使老鼠紋體中BH4濃度和活動量產生週期改變的現象，且BH4濃度與活動量之間存在相反關係。(2)長期持續和斷續性給予安非他命，兩者作用機轉可能不同。(3)安非他命影響活動量和刻板行為的機轉可能不同。(4)BH4亦為研究藥物引起精神症狀的一個重要指標。

〈參考書目〉
彭英次，彭英毅(73)，醫學生理學，合記圖書公司
Andrews,C.D; Fernando, J.C.R.& Curzon, G. (1982) Differential involment of dopamine- containing tracts in 5- hydroxytryptamine dependent behaviours caused by amphetamine in large doses.Neuropharmacology.21,63- 68
Brown,Ronald G.& Segal (1977) Metabolic and experimental actors in the behavioral response to repeated amphetamine. pnarmac. Biochemical Behavior.6,545-552
Bullard,W.P. ,Guthrie,P.E. ,Russo,P.V.& Mandell,A.J (1978)Regional and subcellular distribution and some factors in the regulation of reduced pterins in rat brain. Journal of pharmacology and Experimental Therape 206,4- 20
Builard.,Wilson P. & Mandell,Arnold J. (1980) ,The influence of D-Ampnetamine on rat brain striatal reduced bio- Pterin concentration. Journal of Pharmacology and Experimental Therapetutics.213,3,596-574
Connell,P.H. (1958) Amphetamine Psychosis. London: Chapman and Hill
Costa.:t:.,Guidotti A.& Zivkovic B. (1974) Short- and Long- term regulation of tyrosine hydroxylase. In: Neuropharmacology of Monoamines and Their Regulatory Enzymes (Usdin E., ed)Raven Press, New York
Costa E. & Meek J.L. (1974) Regulation of the biosynthesis of catecholamines and serotonin in the CNS. A. Rev. Pharmac. l4,491-511
Curtius,H.-Ch. & Niederwieser,A. et al (1982) Tetrahydrobiopterin :efficacy in endogenous depression and Parkinson's diease, J. Neural Transmission,55,301-308
Elllson G. & Morris W. (1981) Opposed stages of continuous amphetamine administrations in motor stereotype and in vivo spiroperidol accumulation. European J. of
Pharm.74,207-214
Ellison G. & Ratan R. (1982) The late stage following continous amphetamine administration to rats is correlated with altered dopamine but not serotonin metabolism. Life 801 , 31,771-777
Ellison G. (1983) Phasic alterations in dopamine metabolites follow1ng continous administration of amphetamine. Brain Res.268,387-389
Pukusbrma,7. & Nixon,J.C.(1980),Analysis of reduced forms biopterin in biological tissues and fluids. Anal,Biochem 102,176-188
Gately: Segal,David S.& Geyer,Mark A. (1987) Experimential changes in behavlor induced continuous infusions of amphetamine in rats. Psychopharmacology, 91,217-220
Glick , Stanley D.; Ross,David Alan & Hough, Lindsay B. (1982)Daneral asymmetry of neurotransmitters in human brain. Brain Researon,234,53-63
Guroff,G.,Rhoads,C.A.& Abramowitz,A. (1967) A simple radioisotopic assay for phenylalanine hydroxylase cofactor. Anal.Biochem.21,273-278
Kaufman,S.(1959) studies on the mechanism of the enzymatic, conversion of phenylalanine to tyrosine. J.Biol. Chern. 234, 2677- 2682
Kaufman,S.(1963) The structure of the phenylalanime- hydroxylation cofactor . Proc.Natn.Acad.Sci.U.S.A. 50,1085-10095
Kuczenskl .Ronald(1980)Amphetamine- Haloperidol interactions on striatal and mesolimbic tyrosine hydroxylase activity and aopamine metabolism. Journal of Pharmacology and Experimental Therape,215,1,135-142
Leavitt,F. (1980) Users and abusers of drugs. In:Drugs and Behavior, ediLed by Weiner I.B. New york,165-199
Lee,Eminy H.Y. &Mandell,Arnold J. (1985 a) ,Relationships between drug-induced changes in tetrahydrobiopterin and biogenic amine contrations in rat brain. Journal of Pharmacology and Experimental Therapeatics. 234,1,141-234
Lee,Eminny H.Y. & Mandell,Arnold J. (1985 b) ,Effects of mphetamine on hemispheric asymmetry and regional distributioL or Letra hydroblopterin in rat brain. Neurochem Int.7,9,l-5
Lee,Eminy H.Y. (1987) stress and activity correlated changes of hydroxylase cofactor concentrations in brain tissue and bload. Neurochem Int. 9,1,75-78
Lieth,N.J. & Kuczenskl,R. ( 1981 ) Chronic amphetmine:tolerance and r everse tolerance reflect different behavioral actions of the drus. Pharmac. & Eehavior,15,399-404
Lioyd, T .& Weiner,N . (1971) Isolation and characterization of a tyrosine hydroxylase cofactor from boving adrenal medulla. Mol. Pharmacoi. 7,569-580
Loveenberg,W., Jequier,E.& Sjoerdsma,A. (1967) Tryptophan hydroxylation : Measurement in pineal gland, brain stem and carcinoid tumor. Science.N.Y. 155,217-219
Mandell, A.J., Bullard, Wilson ?, Yellin, Joseph B.& Russo , Patrick A.(1980) The influence or d- amphetamine on rat brain striatal reduced biopterin concentration. The Journal of Pharmacologyand Experimental Therapeutics, 213,3,569-574
Manoell,A.J.& Russo,P.V. (1981) Short- term regulation of hydroxylase cofactor activity in rat brain. Journal of Neurochemistry . 37,1573-1578
Magatsu,T.,Levitt,M.& Undenfrienc,S. (1964) A rapid and simple
radiossay for tyrosine hydroxylase.Anal.Liochem.9,122-126
Nielsen,E (1981) Rapid dec l ine of stereotyped behavior in during constant one week administration of amphetamine implanted ALZET Tm) osmotic minipumps. Pharmacolog Chern. Behavior 15,161-165
Nielsen,Erik B. ;Lee,Tong H.& Ellison Gaylord (1980) Following severals days of continuous administration d- amphetamine acquires hallucinogenlike properties. Psychopharmacology,68,197-200
Oke ,A., Keller.R., Mefford.I.& Adams R.N. (1978) Laterization of norepinephrine in human thalamus. Science. 200, 1411-1413
Randrup,A.& Munkvad,l. (1970) Bi6chemical.anatomical and psychological investigation of stereotyped behavior induceci by amphetamines. In: Amphetamines and Related Compounds,edited by E. Costa and S.Garattini. New York: Raven Press.
Roblson,T.E. & Camp,Dianne M. (1987) Long-lasting effects of escalating does of d-amphetamine on brain monoamines. amphetamine-induced sterotyped behavior and spontaneous noctural iocomotion. Pharmac. Biochem. & Behavior.26,821-827
Sawada,M. et al(1987)Tyrosine hydroxylase,tryptophan hydroxylase, biopterin,and neopterin in the brain of normal controls and patients with senile dementia of Alzheimer Type.J.of Neurochemistry,48,3.760-764
Segal,D.S. & Mandell,A.J. (1974) Long-term andminstration on amphetamine:progressive augmentation of motor avtivity and Steretype. Pharmac Biochemical Behavior.2,2,249-255
Segal.David S.; Weinberger,Susan B.; Cahill,Jerome & McCunney, Stanley J.(1980) Multiple daily amphetamine administration: behavioral and neurochemical alterations. Science. 207,904- 907
Wexier B.F. & Heninger G.R. (1979) Alterations in cerbral laterality during acute psychotic illness. Arch, Gen.Psychiat..36,278-234