对氯苯丙氨酸在动物失眠模型中的应用概述
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摘要
对氯苯丙氨酸作为色氨酸羟化酶抑制剂,可以阻断和耗竭脑内5-羟色胺的合成,导致失眠。近年来,使用对氯苯丙氨酸建立失眠动物模型,因其简单实用、造模效果确切等因素在动物实验中越来越受到学者的认可并被广泛使用。但对氯苯丙氨酸在水中的溶解度较低、悬浮液不易注射,以及在不同动物中使用的剂量和方法不统一等因素阻碍了实验的进展。本文查阅了对氯苯丙氨酸相关研究和使用对氯苯丙氨酸造模的文献,概述了对氯苯丙氨酸在实验中的使用,试图找出使用对氯苯丙氨酸建立失眠动物模型的最佳方法。
Para-chlorophenylalanine( PCPA),a tryptophan hydroxylase inhibitor consumes 5-hydroxytryptamine in the brain that leads to insomnia. In recent years,the establishment of an insomnia animal model using PCPA has been recognized and widely used for animal experiments because of its simplicity and practicality. However,the low solubility of PCPA in water and the difficulty of its injection has hindered the progress of experiments. In this paper,we review literature regarding the use of PCPA,summarize the method for using PCPA in experiments,and discuss the best way to use PCPA.
Para-chlorophenylalanine( PCPA),a tryptophan hydroxylase inhibitor consumes 5-hydroxytryptamine in the brain that leads to insomnia. In recent years,the establishment of an insomnia animal model using PCPA has been recognized and widely used for animal experiments because of its simplicity and practicality. However,the low solubility of PCPA in water and the difficulty of its injection has hindered the progress of experiments. In this paper,we review literature regarding the use of PCPA,summarize the method for using PCPA in experiments,and discuss the best way to use PCPA.
引文
[1] Jouvet M. Sleep and serotonin:an unfinished story[J].Neuropsychopharmacology,1999,21(2):24-27.
[2]美国国家生物技术信息中心. Fenclonine[DB/OL].(2005-3-25)[2018-08-10]. https://pubchem. ncbi. nlm. nih. gov/compound/4652.
[3] Davies JA,Nicholson AN. Studies in the monkey(Macaca mulatta)on the effect of(+/-)-6-fluorotryptophan and(+/-)-p-chlorophenylalanine on plasma tryptophan[proceedings][J].Br J Pharmacol,1978,62(3):451P-452P.
[4] Koe BK, Weissman A. p-Chlorophenylalanine:a specific depletor of brain serotonin[J]. J Pharmacol Exp Ther,1966,154(3):499-516.
[5] Delorme F,Froment JL,Jouvet M. Suppression of sleep with pchloromethamphetamine and p-chlorophenylalanine[J]. C R Seances Soc Biol Fil,1966,160(12):2347-2351.
[6] Rattray M,Baldessari S,Gobbi M,et al. p-Chlorophenylalanine changes serotonin transporter mrna levels and expression of the gene product[J]. J Neurochem,1996,67(2):463-472.
[7] Cremata VY Jr,Koe BK. Clinical-pharmacological evaluation of p-chlorophenylalanine:A new serotonin-depleting agent[J].Clin Pharmacol Ther,1966,7(6),768-776.
[8] O’Connell MT,Portas CM,Sarna GS,et al. Effect of pchlorophenylalanine on release of 5-hydroxytryptamine from the rat frontal cortex in vivo[J]. Br J Pharmacol,1991,102(4):831-836.
[9] Demesquita S. p-Chloroamphetamine:effect on sleep and respiration in the rat[J]. Pharmacol Biochem Behav,1985,22(5):889-891.
[10] Singleton C,Marsden CA. Circadian variation in the head twitch response produced by 5-methoxy-N1,N1-dimethyltryptamine and p-chloroamphetamine in the mouse[J]. Psychopharmacology(Berl),1981,74(2):173-176.
[11] Stracke J,Otten W,Tuchscherer A,et al. Serotonin depletion induces pessimistic-like behavior in a cognitive bias paradigm in pigs[J]. Physiol Behav,2017,174:18-26.
[12] Vataeva LA,Kudrin VS,Vershinina EA,et al. Behavioral alteration in the adult rats prenatally exposed to parachlorophenylalanine[J]. Brain Res,2007,1169(3):9-16.
[13] Vataeva LA,Kudrin VS,Vershinina EA,et al. Maternal parachlorophenylalanine exposure modifies central monoamines and behaviors in the adult offspring[J]. Brain Res,2008,1234(3):1-7.
[14] Deryabina IB,Muranova LN,Andrianov VV,et al. Impairing of serotonin synthesis by p-chlorphenylanine prevents the forgetting of contextual memory after reminder and the protein synthesis inhibition[J]. Front Pharmacol,2018,9:607.
[15] Paxinos G,Burt J,Atrens DM,et al. 5-Hydroxytryptamine depletion with para-chlorophenylalanine:Effects on eating,drinking,irritability,muricide,and copulation[J]. Pharmacol Biochem Behav,1977,6(4):439-447.
[16] Tagliamonte A,Tagliamonte P,Gessa GL,et al. Compulsive sexual activity induced by p-chlorophenylalanine in normal and pinealectomized male rats[J]. Science,1969,166(3911):1433-1435.
[17] Miczek KA, Altman JL, Appel JB, et al. Parachlorophenylalanine, serotonin and killing behavior[J].Pharmacol Biochem Behav,1975,3(3):355-361.
[18] Satterlee WG, Serpick A, Bianchine JR. The carcinoid syndrome:chronic treatment with para-chlorophenylalanine[J].Ann Intern Med,1970,72(6):919-921.
[19]叶超平.类癌综合征临床处理近况[J].临床荟萃,1988(12):18-21.
[20] Gruner W. Exogenous psychosis in a patient with carcinoid syndrome following treatment with p-chlorophenylalanine(PCPA)[J]. Psychiatr Clin(Basel),1975,8(5):266-276.
[21]肖成荣,马增春,李海静,等. PCPA失眠大鼠模型的制作及其机制[J].毒理学杂志,2007(4):326-326.
[22] Borbély AA, Neuhaus HU, Tobler I. Effect of pchlorophenylalanine and tryptophan on sleep,EEG and motor activity in the rat[J]. Behav Brain Res,1981,2(1):1-22.
[23] Park DH,Stone DM,Baker H,et al. Early induction of rat brain tryptophan hydroxylase(TPH)mRNA following parachlorophenylalanine(PCPA)treatment[J]. Brain Res Mol Brain Res,1994,22(1-4):20-28.
[24] Kenton L,Boon F,Cain DP. Combined but not individual administration of beta-adrenergic and serotonergic antagonists impairs water maze acquisition in the rat[J].Neuropsychopharmacology,2008,33(6):1298-1311.
[25] Romaniuk A,Strzelczuk M,Wieczorek M. Further evidence against using sorbitans in the brain mechanisms investigation[J]. Acta Neurobiol Exp(Wars),1990,50(6):619-627.
[26] Fukumoto K,Iijima M,Chaki S. The Antidepressant effects of an m Glu2/3 receptor antagonist and ketamine require AMPA receptor stimulation in the m PFC and subsequent activation of the5-HT neurons in the DRN[J]. Neuropsychopharmacology,2016,41(4):1046-1056.
[27]张林挺.酸枣仁汤对虚劳失眠大鼠干预机理的研究[D].广州:广州中医药大学,2009.
[28] Rai S,Haldar C,Singh R. Modulation of immunity in youngadult and aged squirrel,Funambulus pennanti by melatonin and p-chlorophenylalanine[J]. Immun Ageing,2009,23; 6:5.
[29] Martinez-Cruz F,Osuna C,Guerrero JM. Mitochondrial damage induced by fetal hyperphenylalaninemia in the rat brain and liver:its prevention by melatonin,Vitamin E,and Vitamin C[J]. Neurosci Lett,2006,392(1-2):1-4.
[30] Furlong TM,Leavitt LS,Keefe KA,et al. Methamphetamine-,d-Amphetamine-,and p-chloroamphetamine-induced neurotoxicity differentially effect impulsive responding on the stop-signal task in rats[J]. Neurotox Res,2016,29(4):569-582.
[31] Bobillier P, Froment JL, Seguin S, et al. Effects of pchlorophenylalanine and 5-hydroxytryptophan on sleep and central metabolism of monoamines and proteins of the cat[J].Biochem Pharmacol,1973,22(23):3077-3090.
[32] Doyle RE,Hinch GN,Fisher AD,et al. Administration of serotonin inhibitor p-chlorophenylalanine induces pessimisticlike judgement bias in sheep[J]. Psychoneuroendocrinology,2011,36(2):279-288.
[33] Cuomo V,Marino A. Effects of P-chlorophenylalanine(PCPA)on avoidance conditioning in guinea pigs[J]. Pharmacol Res Commun,1974,6(6):531-537.
[34] Weitzman ED,Rapport MM,Mcgregor P,et al. Sleep patterns of the monkey and brain serotonin concentration:effect of pchlorophenylalanine[J]. Science,1968,160(3834):1361-1363.
[35] Dasari S,Viele K,Turner AC,et al. Influence of PCPA and MDMA(ecstasy)on physiology,development and behavior in drosophilamelanogaster[J]. Eur J Neurosci,2007,26(2):424-438.
[36] Gainutdinov KhL,Andrianov VV,Gainutdinova TKh. The action of the neurotoxins 5, 6-dihydroxytryptamine and pchlorophenylalanine on the electrical activity parameters of the command neurons during long-term sensitization and learning in the snail[J]. Zh Vyssh Nerv Deiat Im I P Pavlova,1999,49(1):48-58.
[37] Wapnir RA,Hawkins RL,Stevenson JH,et al. Effects of oral administration of p-chlorophenylalanine to experimental animals[J]. Biochem Med,1970,3(5):397-403.
[38] Hoyland VJ, Shillito EE, Vogt M. The effect of parachlorophenylalanine on the behaviour of cats[J]. Br J Pharmacol,1970,40(4):659-667.
[39] Keleta YB,Lumia AR,Anderson GM,et al. Behavioral effects of pubertal anabolic androgenic steroid exposure in male rats with low serotonin[J]. Brain Res,2007,1132(1):129-138.
[40] Dyer K, Cain DP. Water maze impairments after combined depletion of somatostatin and serotonin in the rat[J]. Behav Brain Res,2007,181(1):85-95.
[41] Ettrup A,Kornum BR,Weikop P,et al. An approach for serotonin depletion in pigs:Effects on serotonin receptor binding[J]. Synapse,2015,65(2):136-145.
[42] Gao J,Zhang JX,Xu TL. Modulation of serotonergic projection from dorsal raphe nucleus to basolateral amygdala on sleepwaking cycle of rats[J]. Brain Res,2002,945(1):60-70.
[43] Medeiros MA, Costaesousa RH, Olivares EL, et al. A reassessment of the role of serotonergic system in the control of feeding behavior[J]. An Acad Bras Cienc,2005,77(1):103-111.
[44]赵乐章,高隽,张景行,等.中缝背核投射到基底外侧杏仁核的5-羟色胺能纤维对睡眠的调节作用[J].中国药理学通报,2003,19(1):77-79.
[45] Kreiskott H, Hofmann HP. Stimulation of a specific drive(predatory behaviour)by p-chlorophenylalanine(pCPA)in the rat[J]. Pharmakopsychiatr Neuropsychopharmakol,1975,8(3):136-140.
[46] Wapnir RA,Hawkins RL,Stevenson JH,et al. Effects of oral administration of p-chlorophenylalanine to experimental animals[J]. Biochem Med,1970,3(5):397-403.
[47] Herges S,Taylor DA. Modulatory effect of p-chlorophenylalanine microinjected into the dorsal and median raphe nuclei on cocaineinduced behaviour in the rat.[J]. Eur J Pharmacol,1999,374(3):329-340.
[48] Holman RB, Hoyland V, Shillito EE. The failure of pchlorophenylalanine to affect voluntary alcohol consumption in rats[J]. Br J Pharmacol,1975,53(2):299-304.
[49] Ferguson J,Henriksen S,Cohen H,et al.“Hypersexuality”and behavioral changes in cats caused by administration of pchlorophenylalanine[J]. Science,1970,168(3930):499-501.
[50] Miller FP,Cox RH,Snodgrass WR,et al. Comparative effects of p-chloroamphetamine and p-chloro-N-methylamphetamine on rat brain norepinephrine, serotonin and 5-hydroxyindole-3-acetic acid[J]. Biochem Pharmacol,1970,19(2):435-442.
[51] Gross B,Ronen N,Honigman S,et al. Tryptophan toxicity-time and dose response in rats[J]. Adv Exp Med Biol,1999,467:507-516.
[52] Steigrad P, Tobler I, Waser PG, et al. Effect of pchlorophenylalanine on cerebral serotonin binding, serotonin concentration and motor activity in the rat[J]. Naunyn Schmiedebergs Arch Pharmacol,1978,305(2):143-148.
[53] Gralla EJ, Rubin L, et al. Ocular studies with parachlorophenylalanine in rats and monkeys[J]. Arch Ophthalmol,1970,83(6):734-740.
[54] Szeinberg A, Shani M, Crispin M, et al. Inhibition of phenylalanine hydroxylation during treatment of carcinoid syndrome with p-chlorophenylalanine[J]. Isr J Med Sci,1970,6(4):475-478.
[55]李国彰.神经生理学[M].北京:人民卫生出版社,2007:330-335.
[56] Romaniuk A,Strzelczuk M,Wieczorek M. Serotonin depletion with p-chlorophenylalanine in the cat:effects on carbacholinduced defensive behavior and regional brain amine content[J].Acta Neurobiol Exp(Wars),1989,49(4):130-140.
[57] Stokes AH,Xu Y,Daunais JA,et al. p-ethynylphenylalanine:a potent inhibitor of tryptophan hydroxylase[J]. J Neurochem,2000,74(5):2067-2073.
[58] Jéquier E,Lovenberg W,Sjoerdsma A. Tryptophan hydroxylase inhibition:the mechanism by which p-chlorophenylalanine depletes rat brain serotonin[J]. Mol Pharmacol,1967,3(3):274-278.
[59] Zimmer L,Luxen A,Giacomelli F,et al. Short-and long-term effects of p-ethynylphenylalanine on brain serotonin levels[J].Neurochem Res,2002,27(4):269-275.
[2]美国国家生物技术信息中心. Fenclonine[DB/OL].(2005-3-25)[2018-08-10]. https://pubchem. ncbi. nlm. nih. gov/compound/4652.
[3] Davies JA,Nicholson AN. Studies in the monkey(Macaca mulatta)on the effect of(+/-)-6-fluorotryptophan and(+/-)-p-chlorophenylalanine on plasma tryptophan[proceedings][J].Br J Pharmacol,1978,62(3):451P-452P.
[4] Koe BK, Weissman A. p-Chlorophenylalanine:a specific depletor of brain serotonin[J]. J Pharmacol Exp Ther,1966,154(3):499-516.
[5] Delorme F,Froment JL,Jouvet M. Suppression of sleep with pchloromethamphetamine and p-chlorophenylalanine[J]. C R Seances Soc Biol Fil,1966,160(12):2347-2351.
[6] Rattray M,Baldessari S,Gobbi M,et al. p-Chlorophenylalanine changes serotonin transporter mrna levels and expression of the gene product[J]. J Neurochem,1996,67(2):463-472.
[7] Cremata VY Jr,Koe BK. Clinical-pharmacological evaluation of p-chlorophenylalanine:A new serotonin-depleting agent[J].Clin Pharmacol Ther,1966,7(6),768-776.
[8] O’Connell MT,Portas CM,Sarna GS,et al. Effect of pchlorophenylalanine on release of 5-hydroxytryptamine from the rat frontal cortex in vivo[J]. Br J Pharmacol,1991,102(4):831-836.
[9] Demesquita S. p-Chloroamphetamine:effect on sleep and respiration in the rat[J]. Pharmacol Biochem Behav,1985,22(5):889-891.
[10] Singleton C,Marsden CA. Circadian variation in the head twitch response produced by 5-methoxy-N1,N1-dimethyltryptamine and p-chloroamphetamine in the mouse[J]. Psychopharmacology(Berl),1981,74(2):173-176.
[11] Stracke J,Otten W,Tuchscherer A,et al. Serotonin depletion induces pessimistic-like behavior in a cognitive bias paradigm in pigs[J]. Physiol Behav,2017,174:18-26.
[12] Vataeva LA,Kudrin VS,Vershinina EA,et al. Behavioral alteration in the adult rats prenatally exposed to parachlorophenylalanine[J]. Brain Res,2007,1169(3):9-16.
[13] Vataeva LA,Kudrin VS,Vershinina EA,et al. Maternal parachlorophenylalanine exposure modifies central monoamines and behaviors in the adult offspring[J]. Brain Res,2008,1234(3):1-7.
[14] Deryabina IB,Muranova LN,Andrianov VV,et al. Impairing of serotonin synthesis by p-chlorphenylanine prevents the forgetting of contextual memory after reminder and the protein synthesis inhibition[J]. Front Pharmacol,2018,9:607.
[15] Paxinos G,Burt J,Atrens DM,et al. 5-Hydroxytryptamine depletion with para-chlorophenylalanine:Effects on eating,drinking,irritability,muricide,and copulation[J]. Pharmacol Biochem Behav,1977,6(4):439-447.
[16] Tagliamonte A,Tagliamonte P,Gessa GL,et al. Compulsive sexual activity induced by p-chlorophenylalanine in normal and pinealectomized male rats[J]. Science,1969,166(3911):1433-1435.
[17] Miczek KA, Altman JL, Appel JB, et al. Parachlorophenylalanine, serotonin and killing behavior[J].Pharmacol Biochem Behav,1975,3(3):355-361.
[18] Satterlee WG, Serpick A, Bianchine JR. The carcinoid syndrome:chronic treatment with para-chlorophenylalanine[J].Ann Intern Med,1970,72(6):919-921.
[19]叶超平.类癌综合征临床处理近况[J].临床荟萃,1988(12):18-21.
[20] Gruner W. Exogenous psychosis in a patient with carcinoid syndrome following treatment with p-chlorophenylalanine(PCPA)[J]. Psychiatr Clin(Basel),1975,8(5):266-276.
[21]肖成荣,马增春,李海静,等. PCPA失眠大鼠模型的制作及其机制[J].毒理学杂志,2007(4):326-326.
[22] Borbély AA, Neuhaus HU, Tobler I. Effect of pchlorophenylalanine and tryptophan on sleep,EEG and motor activity in the rat[J]. Behav Brain Res,1981,2(1):1-22.
[23] Park DH,Stone DM,Baker H,et al. Early induction of rat brain tryptophan hydroxylase(TPH)mRNA following parachlorophenylalanine(PCPA)treatment[J]. Brain Res Mol Brain Res,1994,22(1-4):20-28.
[24] Kenton L,Boon F,Cain DP. Combined but not individual administration of beta-adrenergic and serotonergic antagonists impairs water maze acquisition in the rat[J].Neuropsychopharmacology,2008,33(6):1298-1311.
[25] Romaniuk A,Strzelczuk M,Wieczorek M. Further evidence against using sorbitans in the brain mechanisms investigation[J]. Acta Neurobiol Exp(Wars),1990,50(6):619-627.
[26] Fukumoto K,Iijima M,Chaki S. The Antidepressant effects of an m Glu2/3 receptor antagonist and ketamine require AMPA receptor stimulation in the m PFC and subsequent activation of the5-HT neurons in the DRN[J]. Neuropsychopharmacology,2016,41(4):1046-1056.
[27]张林挺.酸枣仁汤对虚劳失眠大鼠干预机理的研究[D].广州:广州中医药大学,2009.
[28] Rai S,Haldar C,Singh R. Modulation of immunity in youngadult and aged squirrel,Funambulus pennanti by melatonin and p-chlorophenylalanine[J]. Immun Ageing,2009,23; 6:5.
[29] Martinez-Cruz F,Osuna C,Guerrero JM. Mitochondrial damage induced by fetal hyperphenylalaninemia in the rat brain and liver:its prevention by melatonin,Vitamin E,and Vitamin C[J]. Neurosci Lett,2006,392(1-2):1-4.
[30] Furlong TM,Leavitt LS,Keefe KA,et al. Methamphetamine-,d-Amphetamine-,and p-chloroamphetamine-induced neurotoxicity differentially effect impulsive responding on the stop-signal task in rats[J]. Neurotox Res,2016,29(4):569-582.
[31] Bobillier P, Froment JL, Seguin S, et al. Effects of pchlorophenylalanine and 5-hydroxytryptophan on sleep and central metabolism of monoamines and proteins of the cat[J].Biochem Pharmacol,1973,22(23):3077-3090.
[32] Doyle RE,Hinch GN,Fisher AD,et al. Administration of serotonin inhibitor p-chlorophenylalanine induces pessimisticlike judgement bias in sheep[J]. Psychoneuroendocrinology,2011,36(2):279-288.
[33] Cuomo V,Marino A. Effects of P-chlorophenylalanine(PCPA)on avoidance conditioning in guinea pigs[J]. Pharmacol Res Commun,1974,6(6):531-537.
[34] Weitzman ED,Rapport MM,Mcgregor P,et al. Sleep patterns of the monkey and brain serotonin concentration:effect of pchlorophenylalanine[J]. Science,1968,160(3834):1361-1363.
[35] Dasari S,Viele K,Turner AC,et al. Influence of PCPA and MDMA(ecstasy)on physiology,development and behavior in drosophilamelanogaster[J]. Eur J Neurosci,2007,26(2):424-438.
[36] Gainutdinov KhL,Andrianov VV,Gainutdinova TKh. The action of the neurotoxins 5, 6-dihydroxytryptamine and pchlorophenylalanine on the electrical activity parameters of the command neurons during long-term sensitization and learning in the snail[J]. Zh Vyssh Nerv Deiat Im I P Pavlova,1999,49(1):48-58.
[37] Wapnir RA,Hawkins RL,Stevenson JH,et al. Effects of oral administration of p-chlorophenylalanine to experimental animals[J]. Biochem Med,1970,3(5):397-403.
[38] Hoyland VJ, Shillito EE, Vogt M. The effect of parachlorophenylalanine on the behaviour of cats[J]. Br J Pharmacol,1970,40(4):659-667.
[39] Keleta YB,Lumia AR,Anderson GM,et al. Behavioral effects of pubertal anabolic androgenic steroid exposure in male rats with low serotonin[J]. Brain Res,2007,1132(1):129-138.
[40] Dyer K, Cain DP. Water maze impairments after combined depletion of somatostatin and serotonin in the rat[J]. Behav Brain Res,2007,181(1):85-95.
[41] Ettrup A,Kornum BR,Weikop P,et al. An approach for serotonin depletion in pigs:Effects on serotonin receptor binding[J]. Synapse,2015,65(2):136-145.
[42] Gao J,Zhang JX,Xu TL. Modulation of serotonergic projection from dorsal raphe nucleus to basolateral amygdala on sleepwaking cycle of rats[J]. Brain Res,2002,945(1):60-70.
[43] Medeiros MA, Costaesousa RH, Olivares EL, et al. A reassessment of the role of serotonergic system in the control of feeding behavior[J]. An Acad Bras Cienc,2005,77(1):103-111.
[44]赵乐章,高隽,张景行,等.中缝背核投射到基底外侧杏仁核的5-羟色胺能纤维对睡眠的调节作用[J].中国药理学通报,2003,19(1):77-79.
[45] Kreiskott H, Hofmann HP. Stimulation of a specific drive(predatory behaviour)by p-chlorophenylalanine(pCPA)in the rat[J]. Pharmakopsychiatr Neuropsychopharmakol,1975,8(3):136-140.
[46] Wapnir RA,Hawkins RL,Stevenson JH,et al. Effects of oral administration of p-chlorophenylalanine to experimental animals[J]. Biochem Med,1970,3(5):397-403.
[47] Herges S,Taylor DA. Modulatory effect of p-chlorophenylalanine microinjected into the dorsal and median raphe nuclei on cocaineinduced behaviour in the rat.[J]. Eur J Pharmacol,1999,374(3):329-340.
[48] Holman RB, Hoyland V, Shillito EE. The failure of pchlorophenylalanine to affect voluntary alcohol consumption in rats[J]. Br J Pharmacol,1975,53(2):299-304.
[49] Ferguson J,Henriksen S,Cohen H,et al.“Hypersexuality”and behavioral changes in cats caused by administration of pchlorophenylalanine[J]. Science,1970,168(3930):499-501.
[50] Miller FP,Cox RH,Snodgrass WR,et al. Comparative effects of p-chloroamphetamine and p-chloro-N-methylamphetamine on rat brain norepinephrine, serotonin and 5-hydroxyindole-3-acetic acid[J]. Biochem Pharmacol,1970,19(2):435-442.
[51] Gross B,Ronen N,Honigman S,et al. Tryptophan toxicity-time and dose response in rats[J]. Adv Exp Med Biol,1999,467:507-516.
[52] Steigrad P, Tobler I, Waser PG, et al. Effect of pchlorophenylalanine on cerebral serotonin binding, serotonin concentration and motor activity in the rat[J]. Naunyn Schmiedebergs Arch Pharmacol,1978,305(2):143-148.
[53] Gralla EJ, Rubin L, et al. Ocular studies with parachlorophenylalanine in rats and monkeys[J]. Arch Ophthalmol,1970,83(6):734-740.
[54] Szeinberg A, Shani M, Crispin M, et al. Inhibition of phenylalanine hydroxylation during treatment of carcinoid syndrome with p-chlorophenylalanine[J]. Isr J Med Sci,1970,6(4):475-478.
[55]李国彰.神经生理学[M].北京:人民卫生出版社,2007:330-335.
[56] Romaniuk A,Strzelczuk M,Wieczorek M. Serotonin depletion with p-chlorophenylalanine in the cat:effects on carbacholinduced defensive behavior and regional brain amine content[J].Acta Neurobiol Exp(Wars),1989,49(4):130-140.
[57] Stokes AH,Xu Y,Daunais JA,et al. p-ethynylphenylalanine:a potent inhibitor of tryptophan hydroxylase[J]. J Neurochem,2000,74(5):2067-2073.
[58] Jéquier E,Lovenberg W,Sjoerdsma A. Tryptophan hydroxylase inhibition:the mechanism by which p-chlorophenylalanine depletes rat brain serotonin[J]. Mol Pharmacol,1967,3(3):274-278.
[59] Zimmer L,Luxen A,Giacomelli F,et al. Short-and long-term effects of p-ethynylphenylalanine on brain serotonin levels[J].Neurochem Res,2002,27(4):269-275.