Altered expression of neuronal tryptophan hydroxylase-2 mRNA in the dorsal and median raphe nuclei of three genetically modified mouse models relevant to depression and anxiety

Journal of Chemical Neuroanatomy

Volumn 41, Issue 4, 2011, Pages 227-233

  Jahanshahi, Ali ^a,b,c,d   Le Maitre, Erwan ^a   Temel, Yasin ^b,c,d   Lanfumey, Laurence ^e   Hamon, Michel ^e   Lesch, Klaus Peter ^f   Tordera, Rosa M ^g   Del Río, Joaquín ^g   Aso, Ester ^h   Maldonado, Rafael ^h   Hökfelt, Tomas ^a   Steinbusch, Harry W M ^b,c  

^a KAROLINSKA INSTITUTE   (Sweden)

^b MAASTRICHT UNIVERSITY   (Netherlands)

^c MAASTRICHT UNIVERSITY MEDICAL CENTER   (Netherlands)

^d European Graduate School of Neuroscience   (Netherlands)

^e INSERM   (France)

^f UNIVERSITY OF WÜRZBURG   (Germany)

^g UNIVERSITY OF NAVARRA   (Spain)

^h UNIVERSITAT POMPEU FABRA   (Spain)

Author keywords

Cannabinoid receptor 1; Dorsal raphe nucleus; Glutamate vesicular transporter 1; In situ hybridization; Median raphe nucleus; Serotonin transporter

Indexed keywords

CANNABINOID RECEPTOR; ENDOCANNABINOID; GLUTAMATE TRANSPORTER; GLUTAMIC ACID; MESSENGER RNA; SEROTONIN; TRYPTOPHAN HYDROXYLASE 2;

ALLELE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANXIETY; ARTICLE; CONTROLLED STUDY; DEPRESSION; DORSAL RAPHE NUCLEUS; FEEDBACK SYSTEM; IN SITU HYBRIDIZATION; MALE; MEDIAN RAPHE NUCLEUS; MOUSE; NEUROTRANSMISSION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION;

ANIMALS; ANXIETY; DEPRESSION; IN SITU HYBRIDIZATION; MICE; MICE, KNOCKOUT; MODELS, ANIMAL; NEURONS; RAPHE NUCLEI; RECEPTOR, CANNABINOID, CB1; RNA, MESSENGER; SEROTONIN; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; SYNAPTIC TRANSMISSION; TRYPTOPHAN HYDROXYLASE; VESICULAR GLUTAMATE TRANSPORT PROTEIN 1;

EID: 79960086927     PISSN: 08910618     EISSN: 18736300     Source Type: Journal    
DOI: 10.1016/j.jchemneu.2011.05.015     Document Type: Article

References (90)

1. Abumaria N., Rygula R., Hiemke C., Fuchs E., Havemann-Reinecke U., Ruther E., Flugge G. Effect of chronic citalopram on serotonin-related and stress-regulated genes in the dorsal raphe nucleus of the rat. Eur. Neuropsychopharmacol. 2007, 17:417-429.
2. Aghajanian G.K., Marek G.J. Serotonin, via 5-HT2A receptors, increases EPSCs in layer V pyramidal cells of prefrontal cortex by an asynchronous mode of glutamate release. Brain Res. 1999, 825:161-171.
3. Amargos-Bosch M., Bortolozzi A., Puig M.V., Serrats J., Adell A., Celada P., Toth M., Mengod G., Artigas F. Co-expression and in vivo interaction of serotonin1A and serotonin2A receptors in pyramidal neurons of prefrontal cortex. Cereb. Cortex 2004, 14:281-299.
4. Araneda R., Andrade R. 5-Hydroxytryptamine2 and 5-hydroxytryptamine 1A receptors mediate opposing responses on membrane excitability in rat association cortex. Neuroscience 1991, 40:399-412.
5. Arnsten A.F., Goldman-Rakic P.S. Selective prefrontal cortical projections to the region of the locus coeruleus and raphe nuclei in the rhesus monkey. Brain Res. 1984, 306:9-18.
6. Aso E., Ozaita A., Valdizan E.M., Ledent C., Pazos A., Maldonado R., Valverde O. BDNF impairment in the hippocampus is related to enhanced despair behavior in CB1 knockout mice. J. Neurochem. 2008, 105:565-572.
7. Aso E., Renoir T., Mengod G., Ledent C., Hamon M., Maldonado R., Lanfumey L., Valverde O. Lack of CB1 receptor activity impairs serotonergic negative feedback. J. Neurochem. 2009, 109:935-944.
8. Austin M.C., O'Donnell S.M. Regional distribution and cellular expression of tryptophan hydroxylase messenger RNA in postmortem human brainstem and pineal gland. J. Neurochem. 1999, 72:2065-2073.
9. Bach-Mizrachi H., Underwood M.D., Kassir S.A., Bakalian M.J., Sibille E., Tamir H., Mann J.J., Arango V. Neuronal tryptophan hydroxylase mRNA expression in the human dorsal and median raphe nuclei: major depression and suicide. Neuropsychopharmacology 2006, 31:814-824.
10. Bach-Mizrachi H., Underwood M.D., Tin A., Ellis S.P., Mann J.J., Arango V. Elevated expression of tryptophan hydroxylase-2 mRNA at the neuronal level in the dorsal and median raphe nuclei of depressed suicides. Mol. Psychiatry 2008, 13:507-513.
11. Balschun D., Moechars D., Callaerts-Vegh Z., Vermaercke B., Van Acker N., Andries L., D'Hooge R. Vesicular glutamate transporter VGLUT1 has a role in hippocampal long-term potentiation and spatial reversal learning. Cereb. Cortex 2009, 20:684-693.
12. Bambico F.R., Katz N., Debonnel G., Gobbi G. Cannabinoids elicit antidepressant-like behavior and activate serotonergic neurons through the medial prefrontal cortex. J. Neurosci. 2007, 27:11700-11711.
13. Bengel D., Murphy D.L., Andrews A.M., Wichems C.H., Feltner D., Heils A., Mossner R., Westphal H., Lesch K.P. Altered brain serotonin homeostasis and locomotor insensitivity to 3, 4-methylenedioxymethamphetamine (" Ecstasy" ) in serotonin transporter-deficient mice. Mol. Pharmacol. 1998, 53:649-655.
14. Bhagwagar Z., Wylezinska M., Jezzard P., Evans J., Ashworth F., Sule A., Matthews P.M., Cowen P.J. Reduction in occipital cortex gamma-aminobutyric acid concentrations in medication-free recovered unipolar depressed and bipolar subjects. Biol. Psychiatry 2007, 61:806-812.
15. Bonkale W.L., Turecki G., Austin M.C. Increased tryptophan hydroxylase immunoreactivity in the dorsal raphe nucleus of alcohol-dependent, depressed suicide subjects is restricted to the dorsal subnucleus. Synapse 2006, 60:81-85.
16. Bonkale W.L., Austin M.C. 3,4-Methylenedioxymethamphetamine induces differential regulation of tryptophan hydroxylase 2 protein and mRNA levels in the rat dorsal raphe nucleus. Neuroscience 2008, 155:270-276.
17. Canli T., Lesch K.P. Long story short: the serotonin transporter in emotion regulation and social cognition. Nat. Neurosci. 2007, 10:1103-1109.
18. Celada P., Puig M.V., Casanovas J.M., Guillazo G., Artigas F. Control of dorsal raphe serotonergic neurons by the medial prefrontal cortex: involvement of serotonin-1A, GABA(A), and glutamate receptors. J. Neurosci. 2001, 21:9917-9929.
19. Choudary P.V., Molnar M., Evans S.J., Tomita H., Li J.Z., Vawter M.P., Myers R.M., Bunney W.E., Akil H., Watson S.J., Jones E.G. Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression. Proc. Natl. Acad. Sci. U.S.A. 2005, 102:15653-15658.
20. Clark J.A., Flick R.B., Pai L.Y., Szalayova I., Key S., Conley R.K., Deutch A.Y., Hutson P.H., Mezey E. Glucocorticoid modulation of tryptophan hydroxylase-2 protein in raphe nuclei and 5-hydroxytryptophan concentrations in frontal cortex of C57/Bl6 mice. Mol. Psychiatry 2008, 13:498-506.
21. Clark M.S., McDevitt R.A., Neumaier J.F. Quantitative mapping of tryptophan hydroxylase-2, 5-HT1A, 5-HT1B, and serotonin transporter expression across the anteroposterior axis of the rat dorsal and median raphe nuclei. J. Comp. Neurol. 2006, 498:611-623.
22. Cowen P.J. Serotonin and depression: pathophysiological mechanism or marketing myth?. Trends Pharmacol. Sci. 2008, 29:433-436.
23. Dagerlind A., Friberg K., Bean A.J., Hokfelt T. Sensitive mRNA detection using unfixed tissue: combined radioactive and non-radioactive in situ hybridization histochemistry. Histochemistry 1992, 98:39-49.
24. Dahlstrom A., Fuxe K. Localization of monoamines in the lower brain stem. Experientia 1964, 20:398-399.
25. Fabre V., Beaufour C., Evrard A., Rioux A., Hanoun N., Lesch K.P., Murphy D.L., Lanfumey L., Hamon M., Martres M.P. Altered expression and functions of serotonin 5-HT1A and 5-HT1B receptors in knock-out mice lacking the 5-HT transporter. Eur. J. Neurosci. 2000, 12:2299-2310.
26. Fremeau R.T., Kam K., Qureshi T., Johnson J., Copenhagen D.R., Storm-Mathisen J., Chaudhry F.A., Nicoll R.A., Edwards R.H. Vesicular glutamate transporters 1 and 2 target to functionally distinct synaptic release sites. Science 2004, 304:1815-1819.
27. Garcia-Garcia A.L., Elizalde N., Matrov D., Harro J., Wojcik S.M., Venzala E., Ramirez M.J., Del Rio J., Tordera R.M. Increased vulnerability to depressive-like behavior of mice with decreased expression of VGLUT1. Biol. Psychiatry 2009, 66:275-282.
28. Gardner K.L., Hale M.W., Oldfield S., Lightman S.L., Plotsky P.M., Lowry C.A. Adverse experience during early life and adulthood interact to elevate tph2 mRNA expression in serotonergic neurons within the dorsal raphe nucleus. Neuroscience 2009, 163:991-1001.
29. Gorzalka B.B., Hill M.N., Sun J.C. Functional role of the endocannabinoid system and AMPA/kainate receptors in 5-HT2A receptor-mediated wet dog shakes. Eur. J. Pharmacol. 2005, 516:28-33.
30. Gould G.G., Altamirano A.V., Javors M.A., Frazer A. A comparison of the chronic treatment effects of venlafaxine and other antidepressants on serotonin and norepinephrine transporters. Biol. Psychiatry 2006, 59:408-414.
31. Greenberg P.E., Kessler R.C., Birnbaum H.G., Leong S.A., Lowe S.W., Berglund P.A., Corey-Lisle P.K. The economic burden of depression in the United States: how did it change between 1990 and 2000?. J. Clin. Psychiatry 2003, 64:1465-1475.
32. Gutknecht L., Waider J., Kraft S., Kriegebaum C., Holtmann B., Reif A., Schmitt A., Lesch K.P. Deficiency of brain 5-HT synthesis but serotonergic neuron formation in Tph2 knockout mice. J. Neural Transm. 2008, 115:1127-1132.
33. Gutknecht L., Kriegebaum C., Waider J., Schmitt A., Lesch K.P. Spatio-temporal expression of tryptophan hydroxylase isoforms in murine and human brain: convergent data from Tph2 knockout mice. Eur. Neuropsychopharmacol. 2009, 19:266-282.
34. Haghighi F., Bach-Mizrachi H., Huang Y.Y., Arango V., Shi S., Dwork A.J., Rosoklija G., Sheng H.T., Morozova I., Ju J., Russo J.J., Mann J.J. Genetic architecture of the human tryptophan hydroxylase 2 gene: existence of neural isoforms and relevance for major depression. Mol. Psychiatry 2008, 13:813-820.
35. Hajos M., Richards C.D., Szekely A.D., Sharp T. An electrophysiological and neuroanatomical study of the medial prefrontal cortical projection to the midbrain raphe nuclei in the rat. Neuroscience 1998, 87:95-108.
36. Hajos M., Hajos-Korcsok E., Sharp T. Role of the medial prefrontal cortex in 5-HT1A receptor-induced inhibition of 5-HT neuronal activity in the rat. Br. J. Pharmacol. 1999, 126:1741-1750.
37. Hill M.N., Gorzalka B.B. Is there a role for the endocannabinoid system in the etiology and treatment of melancholic depression?. Behav. Pharmacol. 2005, 16:333-352.
38. Hill M.N., Sun J.C., Tse M.T., Gorzalka B.B. Altered responsiveness of serotonin receptor subtypes following long-term cannabinoid treatment. Int. J. Neuropsychopharmacol. 2006, 9:277-286.
39. Hiroi R., McDevitt R.A., Neumaier J.F. Estrogen selectively increases tryptophan hydroxylase-2 mRNA expression in distinct subregions of rat midbrain raphe nucleus: association between gene expression and anxiety behavior in the open field. Biol. Psychiatry 2006, 60:288-295.
40. Hisano S. Vesicular glutamate transporters in the brain. Anat. Sci. Int. 2003, 78:191-204.
41. Holmes A., Yang R.J., Lesch K.P., Crawley J.N., Murphy D.L. Mice lacking the serotonin transporter exhibit 5-H T1A receptor-mediated abnormalities in tests for anxiety-like behavior. Neuropsychopharmacology 2003, 28:2077-2088.
42. Holmes A., Murphy D.L., Crawley J.N. Abnormal behavioral phenotypes of serotonin transporter knockout mice: parallels with human anxiety and depression. Biol. Psychiatry 2003, 54:953-959.
43. Jankowski M.P., Sesack S.R. Prefrontal cortical projections to the rat dorsal raphe nucleus: ultrastructural features and associations with serotonin and gamma-aminobutyric acid neurons. J. Comp. Neurol. 2004, 468:518-529.
44. Kosofsky B.E., Molliver M.E. The serotoninergic innervation of cerebral cortex: different classes of axon terminals arise from dorsal and median raphe nuclei. Synapse 1987, 1:153-168.
45. Krystal J.H., Sanacora G., Blumberg H., Anand A., Charney D.S., Marek G., Epperson C.N., Goddard A., Mason G.F. Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments. Mol. Psychiatry 2002, 7(Suppl. 1):S71-80.
46. Landgrebe J., Welzl G., Metz T., van Gaalen M.M., Ropers H., Wurst W., Holsboer F. Molecular characterisation of antidepressant effects in the mouse brain using gene expression profiling. J. Psychiatr. Res. 2002, 36:119-129.
47. Lanfumey L., Mannoury La Cour C., Froger N., Hamon M. 5-HT-HPA interactions in two models of transgenic mice relevant to major depression. Neurochem. Res. 2000, 25:1199-1206.
48. Le Poul E., Boni C., Hanoun N., Laporte A.M., Laaris N., Chauveau J., Hamon M., Lanfumey L. Differential adaptation of brain 5-HT1A and 5-HT1B receptors and 5-HT transporter in rats treated chronically with fluoxetine. Neuropharmacology 2000, 39:110-122.
49. Ledent C., Valverde O., Cossu G., Petitet F., Aubert J.F., Beslot F., Bohme G.A., Imperato A., Pedrazzini T., Roques B.P., Vassart G., Fratta W., Parmentier M. Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice. Science 1999, 283:401-404.
50. Lesch K.P., Mossner R. Inactivation of 5HT transport in mice: modeling altered 5HT homeostasis implicated in emotional dysfunction, affective disorders, and somatic syndromes. Handb. Exp. Pharmacol. 2006, 417-456.
51. Lowry C.A., Hale M.W., Evans A.K., Heerkens J., Staub D.R., Gasser P.J., Shekhar A. 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.
52. Maldonado R., Valverde O., Berrendero F. Involvement of the endocannabinoid system in drug addiction. Trends Neurosci. 2006, 29:225-232.
53. Mannoury la Cour C., Boni C., Hanoun N., Lesch K.P., Hamon M., Lanfumey L. Functional consequences of 5-HT transporter gene disruption on 5-HT(1a) receptor-mediated regulation of dorsal raphe and hippocampal cell activity. J. Neurosci. 2001, 21:2178-2185.
54. Martin M., Ledent C., Parmentier M., Maldonado R., Valverde O. Involvement of CB1 cannabinoid receptors in emotional behaviour. Psychopharmacology (Berl.) 2002, 159:379-387.
55. Mato S., Aso E., Castro E., Martin M., Valverde O., Maldonado R., Pazos A. CB1 knockout mice display impaired functionality of 5-HT1A and 5-HT2A/C receptors. J. Neurochem. 2007, 103:2111-2120.
56. Michelsen K.A., Schmitz C., Steinbusch H.W.M. The dorsal raphe nucleus-from silver stainings to a role in depression. Brain Res. Rev. 2007, 55:329-342.
57. Michelsen K.A., Prickaerts J., Steinbusch H.W.M. The dorsal raphe nucleus and serotonin: implications for neuroplasticity linked to major depression and Alzheimer's disease. Prog. Brain Res. 2008, 172:233-264.
58. Murphy D.L., Lesch K.P. Targeting the murine serotonin transporter: insights into human neurobiology. Nat. Rev. Neurosci. 2008, 9(2):85-96.
59. Nakazi M., Bauer U., Nickel T., Kathmann M., Schlicker E. Inhibition of serotonin release in the mouse brain via presynaptic cannabinoid CB1 receptors. Naunyn Schmiedebergs Arch. Pharmacol. 2000, 361:19-24.
60. O'Hearn E., Molliver M.E. Organization of raphe-cortical projections in rat: a quantitative retrograde study. Brain Res. Bull. 1984, 13:709-726.
61. Owens M.J., Nemeroff C.B. The serotonin transporter and depression. Depress. Anxiety 1998, 8(Suppl. 1):5-12.
62. Park D.H., Stone D.M., Baker H., Kim K.S., Joh T.H. Early induction of rat brain tryptophan hydroxylase (TPH) mRNA following parachlorophenylalanine (PCPA) treatment. Brain Res. Mol. Brain Res. 1994, 22:20-28.
63. Paxinos G., Franklin K.B.J. The Mouse Brain Atlas in Stereotaxic Coordinates 2001, Academic Press, San Diego.
64. Peyron C., Petit J.M., Rampon C., Jouvet M., Luppi P.H. Forebrain afferents to the rat dorsal raphe nucleus demonstrated by retrograde and anterograde tracing methods. Neuroscience 1998, 82:443-468.
65. Renoir T., Paizanis E., El Yacoubi M., Saurini F., Hanoun N., Melfort M., Lesch K.P., Hamon M., Lanfumey L. Differential long-term effects of MDMA on the serotoninergic system and hippocampal cell proliferation in 5-HTT knock-out vs. wild-type mice. Int. J. Neuropsychopharmacol. 2008, 11:1149-1162.
66. Rioux A., Fabre V., Lesch K.P., Moessner R., Murphy D.L., Lanfumey L., Hamon M., Martres M.P. Adaptive changes of serotonin 5-HT2A receptors in mice lacking the serotonin transporter. Neurosci. Lett. 1999, 262:113-116.
67. Sanacora G., Gueorguieva R., Epperson C.N., Wu Y.T., Appel M., Rothman D.L., Krystal J.H., Mason G.F. Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression. Arch. Gen. Psychiatry 2004, 61:705-713.
68. Sanchis-Segura C., Cline B.H., Marsicano G., Lutz B., Spanagel R. Reduced sensitivity to reward in CB1 knockout mice. Psychopharmacology (Berl.) 2004, 176:223-232.
69. Schalling M., Seroogy K., Hokfelt T., Chai S.Y., Hallman H., Persson H., Larhammar D., Ericsson A., Terenius L., Graffi J., et al. Neuropeptide tyrosine in the rat adrenal gland-immunohistochemical and in situ hybridization studies. Neuroscience 1988, 24:337-349.
70. Sharp T., Boothman L., Raley J., Queree P. Important messages in the 'post': recent discoveries in 5-HT neurone feedback control. Trends Pharmacol. Sci. 2007, 28:629-636.
71. Shishkina G.T., Kalinina T.S., Dygalo N.N. Up-regulation of tryptophan hydroxylase-2 mRNA in the rat brain by chronic fluoxetine treatment correlates with its antidepressant effect. Neuroscience 2007, 150:404-412.
72. Steinbusch H.W.M. Distribution of serotonin-immunoreactive neurons and their projections in the central nervous system of the rat. Classical Transmitters and Transmitter Receptors in the CNS: Part II. The Handbook of Chemical Neuroanatomy, Vol. 3 1984, 68-125. Elsevier, Amsterdam. A. Björklund, T. Hökfelt, M.J. Kuhar (Eds.).
73. Steinbusch H.W. Distribution of serotonin-immunoreactivity in the central nervous system of the rat-cell bodies and terminals. Neuroscience 1981, 6:557-618.
74. Steinbusch H.W.M., de Vente J. New vistas on the neurobiology of depression: colocalization of serotonin-, dopamine- and nitric oxide synthase-containing neurons in the dorsal raphe nucleus. Depression: Neurobiological, Psychopathological and Therapeutic Advances 1997, 179-196. John Wiley and Sons. A. Honig, H.M. Praag (Eds.).
75. Steinbusch H.W.M., Nieuwenhuys R. The raphe nuclei of the rat brain stem: a cytoarchitectonic and immunohistochemical study using antibodies to serotonin. Chemical Neuroanatomy 1983, 131-207. Raven Press, New York. P. Emson (Ed.).
76. Steinbusch H.W., Nieuwenhuys R., Verhofstad A.A., Van der Kooy D. The nucleus raphe dorsalis of the rat and its projection upon the caudatoputamen. A combined cytoarchitectonic, immunohistochemical and retrograde transport study. J. Physiol. (Paris) 1981, 77:157-174.
77. Takamori S., Rhee J.S., Rosenmund C., Jahn R. Identification of a vesicular glutamate transporter that defines a glutamatergic phenotype in neurons. Nature 2000, 407:189-194.
78. Takamori S. VGLUTs: 'exciting' times for glutamatergic research?. Neurosci. Res. 2006, 55:343-351.
79. Tordera R.M., Totterdell S., Wojcik S.M., Brose N., Elizalde N., Lasheras B., Del Rio J. Enhanced anxiety, depressive-like behaviour and impaired recognition memory in mice with reduced expression of the vesicular glutamate transporter 1 (VGLUT1). Eur. J. Neurosci. 2007, 25:281-290.
80. Tzavara E.T., Davis R.J., Perry K.W., Li X., Salhoff C., Bymaster F.P., Witkin J.M., Nomikos G.G. The CB1 receptor antagonist SR141716A selectively increases monoaminergic neurotransmission in the medial prefrontal cortex: implications for therapeutic actions. Br. J. Pharmacol. 2003, 138:544-553.
81. Uezato A., Meador-Woodruff J.H., McCullumsmith R.E. Vesicular glutamate transporter mRNA expression in the medial temporal lobe in major depressive disorder, bipolar disorder, and schizophrenia. Bipolar Disord. 2009, 11:711-725.
82. Valentine G.W., Sanacora G. Targeting glial physiology and glutamate cycling in the treatment of depression. Biochem. Pharmacol. 2009, 78:431-439.
83. Van Den Bogaert A., Sleegers K., De Zutter S., Heyrman L., Norrback K.F., Adolfsson R., Van Broeckhoven C., Del-Favero J. Association of brain-specific tryptophan hydroxylase TPH2, with unipolar and bipolar disorder in a Northern Swedish, isolated population. Arch. Gen. Psychiatry 2006, 63:1103-1110.
84. Walther D.J., Bader M. A unique central tryptophan hydroxylase isoform. Biochem. Pharmacol. 2003, 66:1673-1680.
85. Weissmann D., Chamba G., Debure L., Rousset C., Richard F., Maitre M., Pujol J.F. Variation of tryptophan-5-hydroxylase concentration in the rat raphe dorsalis nucleus after p-chlorophenylalanine administration: II. Anatomical distribution of the tryptophan-5-hydroxylase protein and regional variation of its turnover rate. Brain Res. 1990, 536:46-55.
86. Wilson N.R., Kang J., Hueske E.V., Leung T., Varoqui H., Murnick J.G., Erickson J.D., Liu G. Presynaptic regulation of quantal size by the vesicular glutamate transporter VGLUT1. J. Neurosci. 2005, 25:6221-6234.
87. Wojcik S.M., Rhee J.S., Herzog E., Sigler A., Jahn R., Takamori S., Brose N., Rosenmund C. An essential role for vesicular glutamate transporter 1 (VGLUT1) in postnatal development and control of quantal size. Proc. Natl. Acad. Sci. U.S.A. 2004, 101:7158-7163.
88. Zhang X., Beaulieu J.M., Sotnikova T.D., Gainetdinov R.R., Caron M.G. Tryptophan hydroxylase-2 controls brain serotonin synthesis. Science 2004, 305:217.
89. Zhou F.M., Hablitz J.J. Activation of serotonin receptors modulates synaptic transmission in rat cerebral cortex. J. Neurophysiol. 1999, 82:2989-2999.
90. Zill P., Baghai T.C., Zwanzger P., Schule C., Eser D., Rupprecht R., Moller H.J., Bondy B., Ackenheil M. SNP and haplotype analysis of a novel tryptophan hydroxylase isoform (TPH2) gene provide evidence for association with major depression. Mol. Psychiatry 2004, 9:1030-1036.