Tryptophan hydroxylase 2 as a therapeutic target for psychiatric disorders: focus on animal models

References

• Jacobs BL, Azmitia EC. Structure and function of the brain serotonin system. Physiol Rev. 1992;72(1):165–229.
   PubMed Web of Science ®Google Scholar
• Gaspar P, Lillesaar C. Probing the diversity of serotonin neurons. Philos Trans R Soc Lond B Biol Sci. 2012;367(1601):2382–2394.
   PubMed Web of Science ®Google Scholar
• Graeff FG, Guimarães FS, De Andrade TG, et al. Role of 5-HT in stress, anxiety, and depression. Pharmacol Biochem Behav. 1996;54(1):129–141.
   PubMed Web of Science ®Google Scholar
• Hale MW, Shekhar A, Lowry CA. Stress-related serotonergic systems: implications for symptomatology of anxiety and affective disorders. Cell Mol Neurobiol. 2012;32(5):695–708.
   PubMed Web of Science ®Google Scholar
• Lesch KP, Waider J. Serotonin in the modulation of neural plasticity and networks: implications for neurodevelopmental disorders. Neuron. 2012;76(1):175–191.
   PubMed Web of Science ®Google Scholar
• Albert VR, Allen JM, Joh TH. A single gene codes for aromatic L-amino acid decarboxylase in both neuronal and non-neuronal tissues. J Biol Chem. 1987;262(19):9404–9411.
   PubMed Web of Science ®Google Scholar
• Walther DJ, Peter JU, Bashammakh S, et al. Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science. 2003;299(5603):76.
   PubMed Web of Science ®Google Scholar
• Walther DJ, Bader M. A unique central tryptophan hydroxylase isoform. Biochem Pharmacol. 2003 Nov 1;66(9):1673–1680. S0006295203005562 [pii]. PubMed PMID: 14563478; eng.
   PubMed Web of Science ®Google Scholar
• Koe BK, Weissman A. p-Chlorophenylalanine: a specific depletor of brain serotonin. J Pharmacol Exp Ther. 1966;154(3):499–516.
   PubMed Web of Science ®Google Scholar
• Kulikov AV, Osipova DV, Naumenko VS, et al. A pharmacological evidence of positive association between mouse intermale aggression and brain serotonin metabolism. Behav Brain Res. 2012;233(1):113–119.
   PubMed Web of Science ®Google Scholar
• Barnes NM, Sharp T. A review of central 5-HT receptors and their function. Neuropharmacology. 1999;38(8):1083–1152.
   PubMed Web of Science ®Google Scholar
• Pytliak M, Vargova V, Mechirova V, et al. Serotonin receptors – from molecular biology to clinical applications. Physiol Res. 2011;60(1):15–25.
   PubMed Web of Science ®Google Scholar
• Barker E, Blakey R. Norepinephrine and serotonin transporters. Molecular targets of antidepressant drugs. In: Bloom E, Kupfer N, editors. Psychopharmacology. The fourth generation of progress. New York: Raven Press; 1995. p. 321–333.
   Google Scholar
• Grouleff J, Ladefoged LK, Koldso H, et al. Monoamine transporters: insights from molecular dynamics simulations. Front Pharmacol. 2015;6:235.
   PubMed Web of Science ®Google Scholar
• Shih JC, Thompson RF. Monoamine oxidase in neuropsychiatry and behavior. Am J Hum Genet. 1999;65(3):593–598.
   PubMed Web of Science ®Google Scholar
• Shih JC, Wu JB, Chen K. Transcriptional regulation and multiple functions of MAO genes. J Neural Transm (Vienna). 2011;118(7):979–986.
   PubMed Web of Science ®Google Scholar
• Lucki I. The spectrum of behavior influenced by serotonin. Biol Psychiatry. 1998;44:151–162.
   PubMed Web of Science ®Google Scholar
• Popova NK. From genes to aggressive behavior: the role of serotonergic system. Bioessays. 2006;28:495–503.
   PubMed Web of Science ®Google Scholar
• Maes M, Meltzer HY. The serotonin hypothesis of major depression. In: Bloom EE, Kupfer NN, editors. Psychopharmacology. The fourth generation of progress. New York (NY): Raven Press; 1995. p. 933–944.
   Google Scholar
• Van Praag HM. Can stress cause depression? Prog Neuropsychopharmacol Biol Psychiatry. 2004;28:891–907.
   PubMed Web of Science ®Google Scholar
• Willner P, Scheel-Krüger J, Belzung C. The neurobiology of depression and antidepressant action. Neurosci Biobehav Rev. 2013;37:2331–2371.
   PubMed Web of Science ®Google Scholar
• Hamon M, Blier P. Monoamine neurocircuitry in depression and strategies for new treatments. Prog Neuropsychopharmacol Biol Psychiatry. 2013;45:54–63.
   PubMed Web of Science ®Google Scholar
• Miller BR, Hen R. The current state of the neurogenic theory of depression and anxiety. Curr Opin Neurobiol. 2015;30:51–58.
   PubMed Web of Science ®Google Scholar
• Gutknecht L, Waider J, Kraft S, et al. Deficiency of brain 5-HT synthesis but serotonergic neuron formation in Tph2 knockout mice. J Neural Transm. 2008;115:1127–1132.
   PubMed Web of Science ®Google Scholar
• Savelieva KV, Zhao S, Pogorelov VM, et al. Genetic disruption of both tryptophan hydroxylase genes dramatically reduces serotonin and affects behavior in models sensitive to antidepressants. PLoS ONE. 2008;3:e3301.
   PubMed Web of Science ®Google Scholar
• Alenina N, Kikic D, Todiras M, et al. Growth retardation and altered autonomic control in mice lacking brain serotonin. Proc Natl Acad Sci USA. 2009;106:10333–10337.
   Web of Science ®Google Scholar
• Popova NK, Kulikov AV. Targeting tryptophan hydroxylase 2 in affective disorder. Expert Opin Ther Targets. 2010;14(11):1259–1271.
   PubMed Web of Science ®Google Scholar
• Matthes S, Mosienko V, Bashammakh S, et al. Tryptophan hydroxylase as novel target for treatment of depressive disorders. Pharmacology. 2010;85:95–109.
   PubMed Web of Science ®Google Scholar
• Kulikov AV, Popova NK. Tryptophan hydroxylase 2 in seasonal affective disorder: underestimated perspectives? Rev Neurosci. 2015;26:679–690.
   PubMed Web of Science ®Google Scholar
• Waider J, Araragi N, Gutknecht L, et al. Tryptophan hydroxylase-2 (TPH2) in disorders of cognitive control and emotion regulation: a perspective. Psychoneuroendocrinology. 2011;36:393–405.
   PubMed Web of Science ®Google Scholar
• Kulikov AV, Gainetdinov RR, Ponimaskin E, et al. Interplay between the key proteins of serotonin system in SSRI antidepressants efficacy. Expert Opin Ther Targets. 2018;22(4):319–330.
   PubMed Web of Science ®Google Scholar
• Ottenhof KW, Sild M, Levesque ML, et al. TPH2 polymorphisms across the spectrum of psychiatric morbidity: asystematic review and meta-analysis. Neurosci Biobehav Rev. 2018;92:29–42.
   PubMed Web of Science ®Google Scholar
• Zhang X, Beaulieu J-M, Gainetdinov RR, et al. Functional polymorphisms of the brain serotonin synthesizing enzyme tryptophan hydroxylase-2. Cell Mol Life Sci. 2006;63:6–11.
   PubMed Web of Science ®Google Scholar
• Zill P, Buttner A, Eisenmenger W, et al. Analysis of tryptophan hydroxylase I and II mRNA expression in the human brain: a post-mortem study. J Psychiatr Res. 2007;41:168–173.
   PubMed Web of Science ®Google Scholar
• Perroud N, Neidhart E, Petit B, et al. Simultaneous analysis of serotonin transporter, thryptophan hydroxylase 1 and 2 gene expression in the ventral prefrontal cortex of suicide victims. Am J Med Genet B. 2010;153B:909–918.
   PubMed Web of Science ®Google Scholar
• Waløen K, Kleppe R, Martinez A, et al. Tyrosine and tryptophan hydroxylases as therapeutic targets in human disease. Expert Opin Ther Targets. 2017;21(2):167–180.
   PubMed Web of Science ®Google Scholar
• Kulikov A, Kozlachkova E, Popova N. The activity of tryptophan hydroxylase in brain of hereditary predisposed to catalepsy rats. Pharmacol Biochem Behav. 1992;43(4):999–1003.
   PubMed Web of Science ®Google Scholar
• Kuhn DM, Sakowski SA, Geddes TJ, et al. Phosphorylation and activation of tryptophan hydroxylase 2: identification of serine-19 as the substrate site for calcium, calmodulin-dependent protein kinase II. J Neurochem. 2007;103(4):1567–1573.
   PubMed Web of Science ®Google Scholar
• Banik U, Wang GA, Wagner PD, et al. Interaction of phosphorylated tryptophan hydroxylase with 14-3-3 proteins. J Biol Chem. 1997;272(42):26219–26225.
   PubMed Web of Science ®Google Scholar
• Mosienko V, Beis D, Pasqualetti M, et al. Life without brain serotonin: reevaluation of serotonin function with mice deficient in brain serotonin synthesis. Behav Brain Res. 2015;277:78–88.
   PubMed Web of Science ®Google Scholar
• Migliarini S, Pacini G, Pelosi B, et al. Lack of brain serotonin affects postnatal development and serotonergic neuronal circuitry formation. Mol Psychiatry. 2013;18(10):1106–1118.
   PubMed Web of Science ®Google Scholar
• Gutknecht L, Araragi N, Merker S, et al. Impacts of brain serotonin deficiency following Tph2 inactivation on development and raphe neuron serotonergic specification. PLoS One. 2012;7(8):e43157.
   PubMed Web of Science ®Google Scholar
• Kane MJ, Angoa-Peréz M, Briggs DI, et al. Mice genetically depleted of brain serotonin display social impairments, communication deficits and repetitive behaviors: possible relevance to autism. PLoS One. 2012;7(11):e48975.
   PubMed Web of Science ®Google Scholar
• Yadav VK, Oury F, Suda N, et al. A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell. 2009;138(5):976–989.
   PubMed Web of Science ®Google Scholar
• Liu Y, Jiang Y, Si Y, et al. Molecular regulation of sexual preference revealed by genetic studies of 5-HT in the brains of male mice. Nature. 2011;472(7341):95–99.
   PubMed Web of Science ®Google Scholar
• Mosienko V, Bert B, Beis D, et al. Exaggerated aggression and decreased anxiety in mice deficient in brain serotonin. Transl Psychiatry. 2012;2:e122.
   PubMed Web of Science ®Google Scholar
• Gutknecht L, Popp S, Waider J, et al. Interaction of brain 5-HT synthesis deficiency, chronic stress and sex differentially impact emotional behavior in Tph2 knockout mice. Psychopharmacology (Berl). 2015;232(14):2429–2441.
   PubMed Web of Science ®Google Scholar
• Song NN, Zhang Q, Huang Y, et al. Enhanced dendritic morphogenesis of adult hippocampal newborn neurons in central 5-HT-deficient mice. Stem Cell Res. 2017;19:6–11.
   PubMed Web of Science ®Google Scholar
• Montalbano A, Waider J, Barbieri M, et al. Cellular resilience: 5-HT neurons in Tph2(-/-) mice retain normal firing behavior despite the lack of brain 5-HT. Eur Neuropsychopharmacol. 2015;25(11):2022–2035.
   PubMed Web of Science ®Google Scholar
• Zhang X, Gainetdinov RR, Beaulieu J-M, et al. Loss-of-function mutation in tryptophan hydroxylase-2 identified in unipolar major depression. Neuron. 2005;45:11–16.
   PubMed Web of Science ®Google Scholar
• Beaulieu JM, Zhang X, Rodriguiz RM, et al. Role of GSK3β in behavioral abnormalities induced by serotonin deficiency. Proc Natl Acad Sci USA. 2008;105:1333–1338.
   PubMed Web of Science ®Google Scholar
• Jacobsen JP, Medvedev IO, Caron MG. The 5-HT deficiency theory of depression: perspectives from a naturalistic 5-HT deficiency model, the tryptophan hydroxylase 2Arg439His knockin mouse. Philos Trans R Soc Lond B Biol Sci. 2012;367(1601):2444–2459.
   PubMed Web of Science ®Google Scholar
• Jacobsen JP, Siesser WB, Sachs BD, et al. Deficient serotonin neurotransmission and depression-like serotonin biomarker alterations in tryptophan hydroxylase 2 (Tph2) loss-of-function mice. Mol Psychiatry. 2012;17(7):694–704.
   PubMed Web of Science ®Google Scholar
• Siesser WB, Sachs BD, Ramsey AJ, et al. Chronic SSRI treatment exacerbates serotonin deficiency in humanized Tph2 mutant mice. ACS Chem Neurosci. 2013;4(1):84–88.
   PubMed Web of Science ®Google Scholar
• Lin YM, Chao SC, Chen TM, et al. Association of functional polymorphisms of the human tryptophan hydroxylase 2 gene with risk for bipolar disorder in Han Chinese. Arch Gen Psychiatry. 2007;64:1015–1024.
   PubMed Web of Science ®Google Scholar
• Scheuch K, Lautenschlager M, Grohmann M, et al. Characterization of a functional promoter polymorphism of the human tryptophan hydroxylase 2 gene in serotonin raphe neurons. Biol Psychiatry. 2007;62:1288–1294.
   PubMed Web of Science ®Google Scholar
• Zhang X, Nichols PJ, Laje G, et al. A functional alternative splicing mutation in human tryptophan hydroxylase 2. Mol Psychiatry. 2011;16:1169–1176.
   PubMed Web of Science ®Google Scholar
• De Luca V, Likhodi O, Van Tol HH, et al. Tryptophan hydroxylase 2 gene expression and promoter polymorphisms in bipolar disorder and schizophrenia. Psychopharmacol. 2005;183:378–382.
   PubMed Web of Science ®Google Scholar
• De Luca V, Likhodi O, Van Tol HH, et al. Gene expression of tryptophan hydroxylase 2 in post-mortem brain of suicide subjects. Int J Neuropsychopharmacol. 2006;9:21–25.
   PubMed Web of Science ®Google Scholar
• Zhang X, Beaulieu JM, Sotnikova TD, et al. Tryptophan hydroxylase-2 controls brain serotonin synthesis. Science. 2004;305:217.
   PubMed Web of Science ®Google Scholar
• Kulikov AV, Osipova DV, Naumenko VS, et al. Association between Tph2 gene polymorphism, brain tryptophan hydroxylase activity and aggressiveness in mouse strains. Genes Brain Behav. 2005;4:482–485.
   PubMed Web of Science ®Google Scholar
• Osipova DV, Kulikov AV, Mekada K, et al. Distribution of the C1473G polymorphism in tryptophan hydroxylase 2 gene in laboratory and wild mice. Genes Brain Behav. 2010;9:537–543.
   PubMed Web of Science ®Google Scholar
• Siesser WB, Zhang X, Jacobsen JP, et al. Tryptophan hydroxylase 2 genotype determines brain serotonin synthesis but not tissue content in C57Bl/6J and BALB/cJ congenic mice. Neurosci Lett. 2010;481:6–11.
   PubMed Web of Science ®Google Scholar
• Osipova DV, Kulikov AV, Popova NK. C1473G polymorphism in mouse tph2 gene is linked to tryptophan hydroxylase-2 activity in the brain, intermale aggression, and depressive-like behavior in the forced swim test. J Neurosci Res. 2009;87(5):1168–1174.
   PubMed Web of Science ®Google Scholar
• Bazovkina DV, Lichman DV, Kulikov AV. The C1473G polymorphism in the tryptophan hydroxylase-2 gene: involvement in ethanol-related behavior in mice. Neurosci Lett. 2015;589:79–82.
   PubMed Web of Science ®Google Scholar
• Koshimizu H, Hirata N, Takao K, et al. Comprehensive behavioral analysis and quantification of brain free amino acids of C57BL/6J congenic mice carrying the 1473G allele in tryptophan hydroxylase-2. Neuropsychopharmacol Rep. 2019;39(1):56–60.
   PubMedGoogle Scholar
• Bazhenova EY, Fursenko DV, Kulikova EA, et al. Effect of photoperiodic alterations on depression-like behavior and the brain serotonin system in mice genetically different in tryptophan hydroxylase 2. Neurosci Lett. 2019;699:91–96.
   PubMed Web of Science ®Google Scholar
• Khotskin N, Bazhenova E, Kulikova E, et al. The effect of the C1473G polymorphism in the tryptophan hydroxylase 2 gene as well as of the daylight period on mice behavior. Zhurn Vyssh Nervn Deyat Im IP Pavlova. 2019;65:85–94.
   Google Scholar
• Khotskin NV, Fursenko DV, Bazovkina DV, et al. Automatic change of special learning characteristics in mice during the water Morris maze test with inverted light. Ros Physiol Zhurnal IM IM Sechenova. 2014;100:36–44.
   PubMedGoogle Scholar
• Bazhenova EY, Bazovkina DV, Kulikova EA, et al. C1473G polymorphism in mouse tryptophan hydroxylase-2 gene in the regulation of the reaction to emotional stress. Neurosci Lett. 2017;640:105–110.
   PubMed Web of Science ®Google Scholar
• Camilleri M. LX-1031, a tryptophan 5-hydroxylase inhibitor, and its potential in chronic diarrhea associated with increased serotonin. Neurogastroenterol Motil. 2011;23(3):193–200.
   PubMed Web of Science ®Google Scholar
• Deguchi T, Barchas J. Comparative studies on the effect of parachlorophenylalanine on hydroxylation of tryptophan in pineal gland and brain of rat. In: Barchas J, Usdin E, editors. Serotonin and behavior. New York (NY): Academic press; 1973. p. 33–48.
   Google Scholar
• Stokes AH, Xu Y, Daunais JA, et al. p-ethynylphenylalanine: a potent inhibitor of tryptophan hydroxylase. J Neurochem. 2000;74(5):2067–2073.
   PubMed Web of Science ®Google Scholar
• Richard F, Sanne JL, Bourde O, et al. Variation of tryptophan-5-hydroxylase concentration in the rat raphe dorsalis nucleus after p-chlorophenylalanine administration. I. A model to study the turnover of the enzymatic protein. Brain Res. 1990;536(1–2):41–45.
   PubMed Web of Science ®Google Scholar
• Zimmer L, Rbah L, Giacomelli F, et al. A reduced extracellular serotonin level increases the 5-HT1A PET ligand 18F-MPPF binding in the rat hippocampus. J Nucl Med. 2003;44(9):1495–1501.
   PubMed Web of Science ®Google Scholar
• Zimmer L, Luxen A, Giacomelli F, et al. Short- and long-term effects of p-ethynylphenylalanine on brain serotonin levels. Neurochem Res. 2002;27(4):269–275.
   PubMed Web of Science ®Google Scholar
• Underhaug J, Aubi O, Martinez A. Phenylalanine hydroxylase misfolding and pharmacological chaperones. Curr Top Med Chem. 2012;12(22):2534–2545.
   PubMed Web of Science ®Google Scholar
• Calvo AC, Scherer T, Pey AL, et al. Effect of pharmacological chaperones on brain tyrosine hydroxylase and tryptophan hydroxylase 2. J Neurochem. 2010;114(3):853–863.
   PubMed Web of Science ®Google Scholar
• Hole M, Jorge-Finnigan A, Underhaug J, et al. Pharmacological chaperones that protect tetrahydrobiopterin dependent aromatic amino acid hydroxylases through different mechanisms. Curr Drug Targets. 2016;17(13):1515–1526.
   PubMed Web of Science ®Google Scholar
• Kure S, Hou DC, Ohura T, et al. Tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency. J Pediatr. 1999;135:375–378.
   PubMed Web of Science ®Google Scholar
• Santos-Sierra S, Kirchmair J, Perna AM, et al. Novel pharmacological chaperones that correct phenylketonuria in mice. Hum Mol Genet. 2012;21(8):1877–1887.
   PubMed Web of Science ®Google Scholar
• Willner P. Animal models of depression: an overview. Pharmacol Ther. 1990;45(3):425–455.
   PubMed Web of Science ®Google Scholar
• Willner P, Mitchell PJ. The validity of animal models of predisposition to depression. Behav Pharmacol. 2002;13(3):169–188.
   PubMed Web of Science ®Google Scholar
• Cryan JF, Mombereau C. In search of a depressed mouse: utility of models for studying depression-related behavior in genetically modified mice. Mol Psychiatry. 2004;9(4):326–357.
   PubMed Web of Science ®Google Scholar
• Cryan JF, Mombereau C, Vassout A. The tail suspension test as a model for assessing antidepressant activity: review of pharmacological and genetic studies in mice. Neurosci Biobehav Rev. 2005;29(4–5):571–625.
   PubMed Web of Science ®Google Scholar
• Shishkina GT, Kalinina TS, Dygalo NN. Up-regulation of tryptophan hydroxylase-2 mRNA in the rat brain by chronic fluoxetine treatment correlates with its antidepressant effect. Neuroscience. 2007;150(2):404–412.
   PubMed Web of Science ®Google Scholar
• Naumenko VS, Kondaurova EM, Bazovkina DV, et al. Effect of brain-derived neurotrophic factor on behavior and key members of the brain serotonin system in genetically predisposed to behavioral disorders mouse strains. Neuroscience. 2012;214:59–67.
   PubMed Web of Science ®Google Scholar
• Naumenko VS, Bazovkina DV, Semenova AA, et al. Effect of glial cell line-derived neurotrophic factor on behavior and key members of the brain serotonin system in mouse strains genetically predisposed to behavioral disorders. J Neurosci Res. 2013;91(12):1628–1638.
   PubMed Web of Science ®Google Scholar
• Browne CA, O’Brien FE, Connor TJ, et al. Differential lipopolysaccharide-induced immune alterations in the hippocampus of two mouse strains: effects of stress. Neuroscience. 2012;225:237–248.
   PubMed Web of Science ®Google Scholar
• Borsini F. Role of the serotonergic system in the forced swimming test. Neurosci Biobehav Rev. 1995;19(3):377–395.
   PubMed Web of Science ®Google Scholar
• Underwood MD, Khaibulina AA, Ellis SP, et al. Morphometry of the dorsal raphe nucleus serotonergic neurons in suicide victims. Biol Psychiatry. 1999;46(4):473–483.
   PubMed Web of Science ®Google Scholar
• Bach-Mizrachi H, Underwood MD, Kassir SA, et al. Neuronal tryptophan hydroxylase mRNA expression in the human dorsal and median raphe nuclei: major depression and suicide. Neuropsychopharmacol. 2006;31:814–824.
   PubMed Web of Science ®Google Scholar
• Bach-Mizrachi H, Underwood MD, Tin A, et al. Evaluated expression of tryptophan hydroxylase-2 mRNA at the neuronal level in the dorsal and median raphe nuclei of depressive suicides. Mol Psychiatry. 2008;13:507–513.
   PubMed Web of Science ®Google Scholar
• Boldrini M, Underwood MD, Mann JJ, et al. More tryptophan hydroxylase in the brainstem dorsal raphe nucleus in depressed suicides. Brain Res. 2005;1041:19–28.
   PubMed Web of Science ®Google Scholar
• Bonkale WL, Turecki G, Austin MC. Increased tryptophan hydroxylase immunoreactivity in the dorsal raphe nucleus of alcohol-dependent, depressive suicide subjects is restricted to the dorsal subnucleus. Synapse. 2006;60:81–85.
   PubMed Web of Science ®Google Scholar
• Lowry CA, Hale MW, Evans AK, et al. Serotonergic systems, anxiety, and affective disorder: focus on the dorsomedial part of the dorsal raphe nucleus. Ann N Y Acad Sci. 2008;1148:86–94.
   PubMed Web of Science ®Google Scholar
• Barton DA, Esler MD, Dawood T, et al. Elevated brain serotonin turnover in patients with depression: effect of genotype and therapy. Arch Gen Psychiatry. 2008;65:38–46.
   PubMed Web of Science ®Google Scholar
• Fitzgerald PJ. Black bile: are elevated monoamines an etiological factor in some cases of major depression? Med Hypotheses. 2013;80(6):823–826.
   PubMed Web of Science ®Google Scholar
• Cervo L, Canetta A, Calcagno E, et al. Genotype-dependent activity of tryptophan hydroxylase-2 determines the response to citalopram in a mouse model of depression. J Neurosci. 2005;25(36):8165–8172.
   PubMed Web of Science ®Google Scholar
• Guzzetti S, Calcagno E, Canetta A, et al. Strain differences in paroxetine-induced reduction of immobility time in the forced swimming test in mice: role of serotonin. Eur J Pharmacol. 2008;594(1–3):117–124.
   PubMed Web of Science ®Google Scholar
• Kulikov AV, Tikhonova MA, Osipova DV, et al. Association between tryptophan hydroxylase-2 genotype and the antidepressant effect of citalopram and paroxetine on immobility time in the forced swim test in mice. Pharmacol Biochem Behav. 2011;99(4):683–687.
   PubMed Web of Science ®Google Scholar
• Carola V, D’Olimpio F, Brunamonti E, et al. Evaluation of the elevated plus-maze and open-field tests for the assessment of anxiety-related behaviour in inbred mice. Behav Brain Res. 2002;134:49–57.
   PubMed Web of Science ®Google Scholar
• Prut L, Belzung C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol. 2003;63:3–33.
   Web of Science ®Google Scholar
• Blier P, Ward NM. Is there a role for 5-HT1A agonists in the treatment of depression? Biol Psychiatry. 2003;53(3):193–203.
   PubMed Web of Science ®Google Scholar
• Akimova E, Lanzenberger R, Kasper S. The serotonin-1A receptor in anxiety disorders. Biol Psychiatry. 2009;66(7):627–635.
   PubMed Web of Science ®Google Scholar
• Celada P, Bortolozzi A, Artigas F. Serotonin 5-HT1A receptors as targets for agents to treat psychiatric disorders: rationale and current status of research. CNS Drugs. 2013;27(9):703–716.
   PubMed Web of Science ®Google Scholar
• Boadle-Biber MC, Corley KC, Graves L, et al. Increase in the activity of tryptophan hydroxylase from cortex and midbrain of male Fischer 344 rats in response to acute or repeated sound stress. Brain Res. 1989;482:306–316.
   PubMed Web of Science ®Google Scholar
• Singh VB, Corley KC, Phan TH, et al. Increases in the activity of tryptophan hydroxylase from rat cortex and midbrain in response to acute or repeated sound stress are blocked by adrenalectomy and restored by dexamethasone treatment. Brain Res. 1990;516:66–76.
   PubMed Web of Science ®Google Scholar
• Singh VB, Onaivi ES, Phan TH, et al. The increases in rat cortical and midbrain tryptophan hydroxylase activity in response to acute or repeated sound stress are blocked by bilateral lesions to the central nucleus of the amygdala. Brain Res. 1990;530:49–53.
   PubMed Web of Science ®Google Scholar
• Shishkina GT, Kalinina TS, Dygalo NN. Serotonergic changes produced by repeated exposure to forced swimming: correlation with behavior. Ann N Y Acad Sci. 2008;1148:148–153.
   PubMed Web of Science ®Google Scholar
• Chamas FM, Underwood MD, Arango V, et al. Immobilization stress elevates tryptophan hydroxylase mRNA and protein in the rat raphe nuclei. Biol Psychiatry. 2004;55:278–283.
   PubMed Web of Science ®Google Scholar
• Bechtholt AJ, Hill TE, Lucki I. Anxiolytic effect of serotonin depletion in the novelty-induced hypophagia test. Psychopharmacology (Berl). 2007;190(4):531–540.
   PubMed Web of Science ®Google Scholar
• Näslund J, Studer E, Nilsson K, et al. Serotonin depletion counteracts sex differences in anxiety-related behaviour in rat. Psychopharmacology (Berl). 2013;230(1):29–35.
   PubMed Web of Science ®Google Scholar
• Whitney MS, Shemery AM, Yaw AM, et al. Adult Brain Serotonin Deficiency Causes Hyperactivity, Circadian Disruption, and Elimination of Siestas. J Neurosci. 2016;36(38):9828–9842.
   PubMed Web of Science ®Google Scholar
• Fernandez SP, Gaspar P. Investigating anxiety and depressive-like phenotypes in genetic mouse models of serotonin depletion. Neuropharmacology. 2012;62(1):144–154.
   PubMed Web of Science ®Google Scholar
• Popova N, Kulikov A, Nikulina E, et al. Serotonin metabolism and serotonergic receptors in Norway rats selected for low aggressiveness to man. Aggressive Behav. 1991;17:207–213.
   Web of Science ®Google Scholar
• Popova N, Voitenko N, Kulikov A, et al. Evidence for the involvement of central serotonin in mechanism of domestication of silver foxes. Pharmacol Biochem Behav. 1991;40:751–756.
   PubMed Web of Science ®Google Scholar
• Powell SB, Zhou X, Geyer MA. Prepulse inhibition and genetic mouse models of schizophrenia. Behav Brain Res. 2009;204(2):282–294.
   PubMed Web of Science ®Google Scholar
• Amann LC, Gandal MJ, Halene TB, et al. Mouse behavioral endophenotypes for schizophrenia. Brain Res Bull. 2010;83(3–4):147–161.
   PubMed Web of Science ®Google Scholar
• Wan L, Thomas Z, Pisipati S, et al. Inhibitory deficits in prepulse inhibition, sensory gating, and antisaccade eye movement in schizotypy. Int J Psychophysiol. 2017;114:47–54.
   PubMed Web of Science ®Google Scholar
• Takahashi H, Kamio Y. Acoustic startle response and its modulation in schizophrenia and autism spectrum disorder in Asian subjects. Schizophr Res. 2018;198:16–20.
   PubMed Web of Science ®Google Scholar
• Fletcher PJ, Selhi ZF, Azampanah A, et al. Reduced brain serotonin activity disrupts prepulse inhibition of the acoustic startle reflex. Effects of 5,7-dihydroxytryptamine and p-chlorophenylalanine. Neuropsychopharmacology. 2001;24(4):399–409.
   PubMed Web of Science ®Google Scholar
• Kostowski W, Gumulka W, Czlonkowski A. Reduced cataleptogenic effects of some neuroleptics in rats with lesioned midbrain raphe and treated with p-chlorophenylalanine. Brain Res. 1972;48:443–446.
   PubMed Web of Science ®Google Scholar
• Kulikov A, Kozlachkova E, Kudryavtseva N, et al. Correlation between tryptophan hydroxylase activity in the brain and predisposition to pinch-induced catalepsy in mice. Pharmacol Biochem Behav. 1995;50:431–435.
   PubMed Web of Science ®Google Scholar
• Albelda N, Joel D. Animal models of obsessive-compulsive disorder: exploring pharmacology and neural substrates. Neurosci Biobehav Rev. 2012;36(1):47–63.
   PubMed Web of Science ®Google Scholar
• Hoffman KL, Cano-Ramírez H. Lost in translation? A critical look at the role that animal models of obsessive compulsive disorder play in current drug discovery strategies. Expert Opin Drug Discov. 2018;13(3):211–220.
   PubMed Web of Science ®Google Scholar
• Muntau AC, Gersting SW. Phenylketonuria as a model for protein misfolding diseases and for the development of next generation orphan drugs for patients with inborn errors of metabolism. J Inherit Metab Dis. 2010;33(6):649–658.
   PubMed Web of Science ®Google Scholar
• Spaapen LJ, Rubio-Gozalbo ME. Tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency, state of the art. Mol Genet Metab. 2003;78(2):93–99.
   PubMed Web of Science ®Google Scholar
• Engelman K, Lovenberg W, Sjoerdsma A. Inhibition of serotonin synthesis by para-chlorophenylalanine in patients with the carcinoid syndrome. N Engl J Med. 1967;277(21):1103–1108.
   PubMed Web of Science ®Google Scholar
• Alfieri AB, Cubeddu LX. Treatment with para-chlorophenylalanine antagonizes the emetic response and the serotonin-releasing actions of cisplatin in cancer patients. Br J Cancer. 1995;71(3):629–632.
   PubMed Web of Science ®Google Scholar
• Shopsin B. The clinical antidepressant effect of exogenous agmatine is not reversed by parachlorophenylalanine: a pilot study. Acta Neuropsychiatr. 2013;25(2):113–118.
   PubMed Web of Science ®Google Scholar