The serotonin system is implicated in major depression and suicide and is negatively regulated by somatodendritic 5-HT1A autoreceptors. Desensitization of 5-HT1A autoreceptors is implicated in the 2- to 3-week latency for antidepressant treatments. Alterations in 5-HT1A receptor levels are reported in depression and suicide, and gene knockout of the 5-HT1A receptor results in an anxiety phenotype, suggesting that abnormal transcriptional regulation of this receptor gene may underlie these disorders. The 5-HT1A receptor gene is negatively regulated in neurons by repressors including REST/NRSF, Freud-1, NUDR/Deaf-1, and Hes5. The association with major depression, suicide, and panic disorder of a new functional 5-HT1A polymorphism at C(-1019)G that selectively blocks repression of the 5-HT1A autoreceptor by NUDR further suggests a causative role for altered regulation of this receptor in predisposition to mental illness. The authors review evidence that altered transcription of the 5-HT1A receptor can affect the serotonin system and limbic and cortical areas, leading to predisposition to depression. NEUROSCIENTIST 10(6):575-593, 2004. DOI:
Abdouh M, Storring JM, Riad M, Paquette Y, Albert PR, Drobetsky E, and others. 2001. Transcriptional mechanisms for induction of 5-HT1A receptor mRNA and protein in activated B and T lymphocytes. J Biol Chem276:4382-4388.
2.
Albert PR, Lembo P, Storring JM, Charest A, Saucier C.1996. The 5-HT1A receptor: signaling, desensitization, and gene transcription. Neuropsychopharmacology14:19-25.
3.
Albert PR, Sajedi N, Lemonde S, Ghahremani MH. 1999. Constitutive G(i2)-dependent activation of adenylyl cyclase type II by the 5-HT1A receptor. Inhibition by anxiolytic partial agonists. J Biol Chem274:35469-35474.
4.
Albert PR, Zhou QY, Van Tol HH, Bunzow JR, Civelli O.1990. Cloning, functional expression, and mRNA tissue distribution of the rat 5-hydroxytryptamine1A receptor gene. J Biol Chem265:5825-5832.
5.
Altar CA, Laeng P, Jurata LW, Brockman JA, Lemire A, Bullard J, and others. 2004. Electroconvulsive seizures regulate gene expression of distinct neurotrophic signaling pathways. J Neurosci24:2667-2677.
6.
Arango V, Huang Y, Underwood MD, Mann JJ. 2003. Genetics of the serotonergic system in suicidal behavior. J Psychiatr Res37:375-386.
7.
Arango V, Underwood MD, Boldrini M, Tamir H, Kassir SA, Hsiung S, and others. 2001. Serotonin 1A receptors, serotonin transporter binding and serotonin transporter mRNA expression in the brainstem of depressed suicide victims. Neuropsychopharmacology25:892-903.
8.
Arborelius L, Linner L, Wallsten C, Ahlenius S, Svensson TH. 2000. Partial 5-HT1A receptor agonist properties of (-)pindolol in combination with citalopram on serotonergic dorsal raphe cell firing in vivo. Psychopharmacology (Berl)151:77-84.
9.
Arias B, Arranz MJ, Gasto C, Catalan R, Pintor L, Gutierrez B, and others. 2002. Analysis of structural polymorphisms and C-1018G promoter variant of the 5-HT(1A) receptor gene as putative risk factors in major depression. Mol Psychiatry7:930-932.
10.
Arias B, Arranz MJ, Gasto C, Catalan R, Pintor L, Gutierrez B, and others. 2003. Analysis of structural polymorphisms and C-1018G promoter variant of the 5-HT(1A) receptor gene as putative risk factors in major depression. Mol Psychiatry8:246.
11.
Artigas F, Celada P, Laruelle M, Adell A.2001. How does pindolol improve antidepressant action?Trends Pharmacol Sci22:224-228.
12.
Artigas F, Romero L, de Montigny C, Blier P.1996. Acceleration of the effect of selected antidepressant drugs in major depression by 5-ht1a antagonists. Trends Neurosci19:378-383.
13.
Austin MC, Whitehead RE, Edgar CL, Janosky JE, Lewis DA. 2002. Localized decrease in serotonin transporter-immunoreactive axons in the prefrontal cortex of depressed subjects committing suicide. Neuroscience114:807-815.
14.
Azmitia EC. 2001. Modern views on an ancient chemical: serotonin effects on cell proliferation, maturation, and apoptosis. Brain Res Bull56:413-424.
15.
Aznar S, Qian Z, Shah R, Rahbek B, Knudsen GM. 2003. The 5-HT1A serotonin receptor is located on calbindin- and parvalbumin-containing neurons in the rat brain. Brain Res959:58-67.
16.
Barnes NM, Sharp T.1999. A review of central 5-HT receptors and their function. Neuropharmacology38:1083-1152.
17.
Benninghoff J, Schmitt A, Mossner R, Lesch KP. 2002. When cells become depressed: focus on neural stem cells in novel treatment strategies against depression. J Neural Transm109:947-962.
18.
Berrettini WH. 2000. Genetics of psychiatric disease. Annu Rev Med51:465-479.
19.
Blier P, de Montigny C.1999. Serotonin and drug-induced therapeutic responses in major depression, obsessive-compulsive and panic disorders. Neuropsychopharmacology21:91S-98S.
20.
Blier P, Ward NM. 2003. Is there a role for 5-HT(1A) agonists in the treatment of depression?Biol Psychiatry53:193-203.
21.
Bottomley MJ, Collard MW, Huggenvik JI, Liu Z, Gibson TJ, Sattler M.2001. The SAND domain structure defines a novel DNA-binding fold in transcriptional regulation. Nat Struct Biol8: 626-633.
22.
Bremner JD, Vythilingam M, Vermetten E, Vaccarino V, Charney DS. 2004. Deficits in hippocampal and anterior cingulate functioning during verbal declarative memory encoding in midlife major depression. Am J Psychiatry161:637-645.
23.
Burnet PW, Eastwood SL, Harrison PJ. 1997. [3H]WAY-100635 for 5-HT1A receptor autoradiography in human brain: a comparison with [3H]8-OH-DPAT and demonstration of increased binding in the frontal cortex in schizophrenia. Neurochem Int30:565-574.
24.
Campbell S, Marriott M, Nahmias C, MacQueen GM. 2004. Lower hippocampal volume in patients suffering from depression: a meta-analysis. Am J Psychiatry161:598-607.
25.
Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, and others. 2003. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science301:386-389.
26.
Celada P, Puig MV, Casanovas JM, Guillazo G, Artigas F.2001. Control of dorsal raphe serotonergic neurons by the medial prefrontal cortex: Involvement of serotonin-1A, GABA(A), and glutamate receptors. J Neurosci21:9917-9929.
27.
Champoux M, Bennett A, Shannon C, Higley JD, Lesch KP, Suomi SJ. 2002. Serotonin transporter gene polymorphism, differential early rearing, and behavior in rhesus monkey neonates. Mol Psychiatry7:1058-1063.
28.
Charest A, Wainer BH, Albert PR. 1993. Cloning and differentiation-induced expression of a murine serotonin1A receptor in a septal cell line. J Neurosci13:5164-5171.
29.
Charney DS, Krystal JH, Delgado PL, Heninger GR. 1990. Serotonin-specific drugs for anxiety and depressive disorders. Annu Rev Med41:437-446.
30.
Chinnadurai G.2002. CtBP, an unconventional transcriptional core-pressor in development and oncogenesis. Mol Cell9:213-224.
31.
Clarke WP, Yocca FD, Maayani S.1996. Lack of 5-hydroxytrypta-mine1A-mediated inhibition of adenylyl cyclase in dorsal raphe of male and female rats. J Pharmacol Exp Ther277:1259-1266.
32.
Conti AC, Cryan JF, Dalvi A, Lucki I, Blendy JA. 2002. cAMP response element-binding protein is essential for the upregulation of brain-derived neurotrophic factor transcription, but not the behavioral or endocrine responses to antidepressant drugs. J Neurosci22:3262-3268.
33.
Coyle JT, Duman RS. 2003. Finding the intracellular signaling pathways affected by mood disorder treatments. Neuron38:157-160.
34.
Del Tredici AL, Schiffer HH, Burstein ES, Lameh J, Mohell N, Hacksell U, and others. 2004. Pharmacology of polymorphic variants of the human 5-HT1A receptor. Biochem Pharmacol67:479-490.
35.
Doris A, Ebmeier K, Shajahan P.1999. Depressive illness. Lancet354:1369-1375.
36.
Drevets WC, Frank E, Price JC, Kupfer DJ, Greer PJ, Mathis C.2000. Serotonin type-1A receptor imaging in depression. Nucl Med Biol27:499-507.
37.
Drevets WC, Frank E, Price JC, Kupfer DJ, Holt D, Greer PJ, and others. 1999. PET imaging of serotonin 1A receptor binding in depression. Biol Psychiatry46:1375-1387.
38.
Duman RS. 2004. Role of neurotrophic factors in the etiology and treatment of mood disorders. Neuromol Med5:11-26.
39.
Erdmann J, Shimron-Abarbanell D, Cichon S, Albus M, Maier W, Lichtermann D, and others. 1995. Systematic screening for mutations in the promoter and the coding region of the 5-HT1A gene. Am J Med Genet60:393-399.
40.
Fabel K, Tam B, Kaufer D, Baiker A, Simmons N, Kuo CJ, and others. 2003. VEGF is necessary for exercise-induced adult hippocampal neurogenesis. Eur J Neurosci18:2803-2812.
41.
Faber KM, Haring JH. 1999. Synaptogenesis in the postnatal rat fascia dentata is influenced by 5-HT1a receptor activation. Brain Res Dev Brain Res114:245-252.
42.
Fabre V, Beaufour C, Evrard A, Rioux A, Hanoun N, Lesch KP, and others. 2000. Altered expression and functions of serotonin 5-HT1A and 5-HT1B receptors in knock-out mice lacking the 5-HT transporter. Eur J Neurosci12:2299-2310.
43.
Fava M, Kendler KS. 2000. Major depressive disorder. Neuron28:335-341.
44.
Ferguson SS. 2001. Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling. Pharmacol Rev53:1-24.
45.
Frodl T, Meisenzahl EM, Zill P, Baghai T, Rujescu D, Leinsinger G, and others. 2004. Reduced hippocampal volumes associated with the long variant of the serotonin transporter polymorphism in major depression. Arch Gen Psychiatry61:177-183.
46.
Fuks F, Hurd PJ, Wolf D, Nan X, Bird AP, Kouzarides T.2003. The methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation. J Biol Chem278:4035-4040.
47.
Galter D, Unsicker K.2000. Sequential activation of the 5-HT1(A) serotonin receptor and TrkB induces the serotonergic neuronal phenotype. Mol Cell Neurosci15:446-455.
48.
Gobbi G, Murphy DL, Lesch K, Blier P.2001. Modifications of the serotonergic system in mice lacking serotonin transporters: an in vivo electrophysiological study. J Pharmacol Exp Ther296:987-995.
49.
Greden JF. 2001. The burden of recurrent depression: causes, consequences, and future prospects. J Clin Psychiatry62:5-9.
50.
Gross C, Zhuang X, Stark K, Ramboz S, Oosting R, Kirby L, and others. 2002. Serotonin1A receptor acts during development to establish normal anxiety-like behaviour in the adult. Nature416:396-400.
51.
Gur E, Dremencov E, Garcia F, Van de Kar LD, Lerer B, Newman ME. 2002. Functional effects of chronic electroconvulsive shock on serotonergic 5-HT(1A) and 5-HT(1B) receptor activity in rat hippocampus and hypothalamus. Brain Res952:52-60.
52.
Gur E, Lerer B, Dremencov E, Newman ME. 2000. Chronic repetitive transcranial magnetic stimulation induces subsensitivity of presynaptic serotonergic autoreceptor activity in rat brain. Neuroreport11:2925-2929.
53.
Gur E, Lifschytz T, Lerer B, Newman ME. 2002. Effects of triiodothyronine and imipramine on basal 5-HT levels and 5-HT(1) autoreceptor activity in rat cortex. Eur J Pharmacol457:37-43.
54.
Haddjeri N, de Montigny C, Blier P.1999. Modulation of the firing activity of rat serotonin and noradrenaline neurons by (+/-)pindolol. Biol Psychiatry45:1163-1169.
55.
Hahm K, Sum EY, Fujiwara Y, Lindeman GJ, Visvader JE, Orkin SH. 2004. Defective neural tube closure and anteroposterior patterning in mice lacking the LIM protein LMO4 or its interacting partner Deaf-1. Mol Cell Biol24:2074-2082.
56.
Hajos M, Hajos-Korcsok E, Sharp T.1999. Role of the medial prefrontal cortex in 5-HT1A receptor-induced inhibition of 5-HT neuronal activity in the rat. Br J Pharmacol126:1741-1750.
Hanley NR, Van de Kar LD. 2003. Serotonin and the neuroendocrine regulation of the hypothalamic—pituitary-adrenal axis in health and disease. Vitam Horm66:189-255.
59.
Hariri AR, Mattay VS, Tessitore A, Kolachana B, Fera F, Goldman D, and others. 2002. Serotonin transporter genetic variation and the response of the human amygdala. Science297:400-403.
60.
He M, Sibille E, Benjamin D, Toth M, Shippenberg T.2001. Differential effects of 5-HT1A receptor deletion upon basal and fluoxetine-evoked 5-HT concentrations as revealed by in vivo microdialysis. Brain Res902:11-17.
61.
Heisler LK, Chu HM, Brennan TJ, Danao JA, Bajwa P, Parsons LH, and others. 1998. Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor mutant mice. Proc Natl Acad Sci U S A95:15049-15054.
62.
Hendricks T, Francis N, Fyodorov D, Deneris ES. 1999. The ETS domain factor Pet-1 is an early and precise marker of central serotonin neurons and interacts with a conserved element in serotonergic genes. J Neurosci19:10348-10356.
63.
Hendricks TJ, Fyodorov DV, Wegman LJ, Lelutiu NB, Pehek EA, Yamamoto B, and others. 2003. Pet-1 ETS gene plays a critical role in 5-HT neuron development and is required for normal anxiety-like and aggressive behavior. Neuron37:233-247.
64.
Hensler JG, Ladenheim EE, Lyons WE. 2003. Ethanol consumption and serotonin-1A (5-HT1A) receptor function in heterozygous BDNF (+/-) mice. J Neurochem85:1139-1147.
65.
Hervas I, Vilaro MT, Romero L, Scorza MC, Mengod G, Artigas F.2001. Desensitization of 5-HT(1A) autoreceptors by a low chronic fluoxetine dose effect of the concurrent administration of WAY-100635. Neuropsychopharmacology24:11-20.
66.
Hjorth S, Bengtsson HJ, Kullberg A, Carlzon D, Peilot H, Auerbach SB. 2000. Serotonin autoreceptor function and antidepressant drug action. J Psychopharmacol14:177-185.
67.
Holmes A, Murphy DL, Crawley JN. 2003. Abnormal behavioral phenotypes of serotonin transporter knockout mice: parallels with human anxiety and depression. Biol Psychiatry54:953-959.
68.
Hoyer D, Martin G.1997. 5-HT receptor classification and nomenclature: towards a harmonization with the human genome. Neuropharmacology36:419-428.
69.
Hsiung SC, Adlersberg M, Arango V, Mann JJ, Tamir H, Liu KP. 2003. Attenuated 5-HT1A receptor signaling in brains of suicide victims: involvement of adenylyl cyclase, phosphatidylinositol 3-kinase, Akt and mitogen-activated protein kinase. J Neurochem87:182-194.
70.
Hyman S.2000. Mental illness: genetically complex disorders of neural circuitry and neural communication. Neuron28:321-323.
71.
Jacobs BL, Azmitia EC. 1992. Structure and function of the brain serotonin system. Physiol Rev72:165-229.
72.
Johansson C, Jansson M, Linner L, Yuan QP, Pedersen NL, Blackwood D, and others. 2001. Genetics of affective disorders. Eur Neuropsychopharmacol11:385-394.
73.
Kageyama R, Ohtsuka T.1999. The Notch-Hes pathway in mammalian neural development. Cell Res9:179-188.
74.
Kawanishi Y, Harada S, Tachikawa H, Okubo T, Shiraishi H.1998. Novel mutations in the promoter and coding region of the human 5-HT1A receptor gene and association analysis in schizophrenia. Am J Med Genet81:434-439.
75.
Lee HJ, Elliot GJ, Hammond DN, Lee VM, Wainer BH. 1991. Constitutive expression of the mature array of neurofilament proteins by a CNS neuronal cell line. Brain Res558:197-208.
76.
Lee SJ, McEwen BS. 2001. Neurotrophic and neuroprotective actions of estrogens and their therapeutic implications. Annu Rev Pharmacol Toxicol41:569-591.
77.
Lemonde S, Rogaeva A, Albert PR. 2004. Cell type-dependent recruitment of trichostatin A-sensitive repression of the human 5-HT1A receptor gene. J Neurochem88:857-868.
78.
Lemonde S, Turecki G, Bakish D, Du L, Hrdina PD, Bown CD, and others. 2003. Impaired repression at a 5-hydroxytryptamine 1A receptor gene polymorphism associated with major depression and suicide. J Neuroscience23:8788-8799.
79.
Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, and others. 1996. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region [see comments]. Science274:1527-1531.
80.
Lesch KP, Heils A.2000. Serotonergic gene transcriptional control regions: targets for antidepressant drug development?Int J Neuropsychopharmacol3:67-79.
81.
Lesch KP, Zeng Y, Reif A, Gutknecht L.2003. Anxiety-related traits in mice with modified genes of the serotonergic pathway. Eur J Pharmacol480:185-204.
82.
Liu D, Diorio J, Day JC, Francis DD, Meaney MJ. 2000. Maternal care, hippocampal synaptogenesis and cognitive development in rats. Nat Neurosci3:799-806.
83.
Lopez JF, Chalmers DT, Little KY, Watson SJ. 1998. A.E. Bennett Research Award. Regulation of serotonin1A, glucocorticoid, and mineralocorticoid receptor in rat and human hippocampus: implications for the neurobiology of depression. Biol Psychiatry43:547-573.
84.
Lopez JF, Liberzon I, Vazquez DM, Young EA, Watson SJ. 1999. Serotonin 1A receptor messenger RNA regulation in the hippocampus after acute stress. Biol Psychiatry45:934-937.
85.
Lopez-Figueroa AL, Norton CS, Lopez-Figueroa MO, Armellini-Dodel D, Burke S, Akil H, and others. 2004. Serotonin 5-HT1A, 5-HT1B, and 5-HT2A receptor mRNA expression in subjects with major depression, bipolar disorder, and schizophrenia. Biol Psychiatry55:225-233.
86.
MacQueen GM, Campbell S, McEwen BS, Macdonald K, Amano S, Joffe RT, and others. 2003. Course of illness, hippocampal function, and hippocampal volume in major depression. Proc Natl Acad Sci U S A100:1387-1392.
87.
Malberg JE, Duman RS. 2003. Cell proliferation in adult hippocampus is decreased by inescapable stress: reversal by fluoxetine treatment. Neuropsychopharmacology28:1562-1571.
88.
Malberg JE, Eisch AJ, Nestler EJ, Duman RS. 2000. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci20:9104-9110.
89.
Mann JJ, Huang YY, Underwood MD, Kassir SA, Oppenheim S, Kelly TM, and others. 2000. A serotonin transporter gene promoter polymorphism (5-HTTLPR) and prefrontal cortical binding in major depression and suicide. Arch Gen Psychiatry57:729-738.
90.
Mannoury la Cour C, Boni C, Hanoun N, Lesch KP, Hamon M, Lanfumey L.2001. Functional consequences of 5-HT transporter gene disruption on 5-HT(1a) receptor-mediated regulation of dorsal raphe and hippocampal cell activity. J Neurosci21:2178-2185.
91.
Martin-Ruiz R, Puig MV, Celada P, Shapiro DA, Roth BL, Mengod G, and others. 2001. Control of serotonergic function in medial prefrontal cortex by serotonin-2A receptors through a glutamate-dependent mechanism. J Neurosci21:9856-9866.
92.
Martinez D, Hwang D, Mawlawi O, Slifstein M, Kent J, Simpson N, and others. 2001. Differential occupancy of somatodendritic and postsynaptic 5HT(1A) receptors by pindolol: a dose-occupancy study with [11C]WAY 100635 and positron emission tomography in humans. Neuropsychopharmacology24:209-229.
93.
Matsuda A, Suzuki Y, Honda G, Muramatsu S, Matsuzaki O, Nagano Y, and others. 2003. Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways. Oncogene22:3307-3318.
94.
Mayberg HS. 2003. Modulating dysfunctional limbic-cortical circuits in depression: towards development of brain-based algorithms for diagnosis and optimised treatment. Br Med Bull65:193-207.
95.
McEwen BS. 1999. Stress and hippocampal plasticity. Annu Rev Neurosci22:105-122.
96.
McEwen BS. 2001. Plasticity of the hippocampus: adaptation to chronic stress and allostatic load. Ann N Y Acad Sci933:265-277.
97.
Meaney MJ. 2001. Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annu Rev Neurosci24:1161-1192.
98.
Meijer OC, de Kloet ER. 1998. Corticosterone and serotonergic neurotransmission in the hippocampus: functional implications of central corticosteroid receptor diversity. Crit Rev Neurobiol12:1-20.
99.
Mendelson SD, McEwen BS. 1992. Quantitative autoradiographic analyses of the time course and reversibility of corticosterone-induced decreases in binding at 5-HT1A receptors in rat forebrain. Neuroendocrinology56:881-888.
100.
Michelson RJ, Collard MW, Ziemba AJ, Persinger J, Bartholomew B, Huggenvik JI. 1999. Nuclear DEAF-1-related (NUDR) protein contains a novel DNA binding domain and represses transcription of the heterogeneous nuclear ribonucleoprotein A2/B1 promoter. J Biol Chem274:30510-30519.
101.
Miller HL, Delgado PL, Salomon RM, Licinio J, Barr LC, Charney DS. 1992. Acute tryptophan depletion: a method of studying anti-depressant action. J Clin Psychiatry53(Suppl):28-35.
102.
Moore P, Landolt HP, Seifritz E, Clark C, Bhatti T, Kelsoe J, and others. 2000. Clinical and physiological consequences of rapid tryptophan depletion. Neuropsychopharmacology23:601-622.
103.
Moreno FA, Rowe DC, Kaiser B, Chase D, Michaels T, Gelernter J, and others. 2002. Association between a serotonin transporter promoter region polymorphism and mood response during tryptophan depletion. Mol Psychiatry7:213-216.
104.
Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM. 2002. Neurobiology of depression. Neuron34:13-25.
105.
Neumeister A, Bain E, Nugent AC, Carson RE, Bonne O, Luckenbaugh DA, and others. 2004. Reduced serotonin type 1A receptor binding in panic disorder. J Neurosci24:589-591.
106.
Neumeister A, Konstantinidis A, Stastny J, Schwarz MJ, Vitouch O, Willeit M, and others. 2002. Association between serotonin transporter gene promoter polymorphism (5HTTLPR) and behavioral responses to tryptophan depletion in healthy women with and without family history of depression. Arch Gen Psychiatry59:613-620.
107.
Ou XM, Jafar-Nejad H, Storring JM, Meng JH, Lemonde S, Albert PR. 2000. Novel dual repressor elements for neuronal cell-specific transcription of the rat 5-HT1A receptor gene. J Biol Chem275:8161-8168.
108.
Ou XM, Lemonde S, Jafar-Nejad H, Bown CD, Goto A, Rogaeva A, and others. 2003. Freud-1: a novel calcium-regulated repressor of the 5-HT1A receptor gene. J Neurosci23:7415-7425.
109.
Ou XM, Storring JM, Kushwaha N, Albert PR. 2001. A novel negative response element for transrepression of the 5-HT1A receptor gene by mineralocorticoid/glucocorticoid receptor heterodimerization. J Biol Chem276:14299-14307.
110.
Parks CL, Robinson PS, Sibille E, Shenk T, Toth M.1998. Increased anxiety of mice lacking the serotonin1A receptor. Proc Natl Acad Sci U S A95:10734-10739.
111.
Parks CL, Shenk T.1996. The serotonin 1a receptor gene contains a TATA-less promoter that responds to MAZ and Sp1. J Biol Chem271:4417-4430.
Pineyro G, Blier P.1999. Autoregulation of serotonin neurons: role in antidepressant drug action. Pharmacol Rev51:533-591.
114.
Rabiner EA, Gunn RN, Castro ME, Sargent PA, Cowen PJ, Koepp MJ, and others. 2000. Beta-blocker binding to human 5-HT(1A) receptors in vivo and in vitro: implications for antidepressant therapy. Neuropsychopharmacology23:285-293.
115.
Rajkowska G.2000. Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells. Biol Psychiatry48:766-777.
116.
Rajkowska G.2003. Depression: what we can learn from postmortem studies. Neuroscientist9:273-284.
117.
Ramboz S, Oosting R, Amara DA, Kung HF, Blier P, Mendelsohn M, and others. 1998. Serotonin receptor 1A knockout: an animal model of anxiety-related disorder. Proc Natl Acad Sci U S A95:14476-14481.
118.
Raymond JR, Mukhin YV, Gettys TW, Garnovskaya MN. 1999. The recombinant 5-HT1A receptor: G protein coupling and signalling pathways. Br J Pharmacol127:1751-1764.
119.
Reif A, Lesch KP. 2003. Toward a molecular architecture of personality. Behav Brain Res139:1-20.
120.
Riad M, Garcia S, Watkins KC, Jodoin N, Doucet E, Langlois X, and others. 2000. Somatodendritic localization of 5-HT1A and preterminal axonal localization of 5-HT1B serotonin receptors in adult rat brain. J Comp Neurol417:181-194.
121.
Riad M, Watkins KC, Doucet E, Hamon M, Descarries L.2001. Agonist-induced internalization of serotonin-1a receptors in the dorsal raphe nucleus (autoreceptors) but not hippocampus (heteroreceptors). J Neurosci21:8378-8386.
122.
Rothe C, Gutknecht L, Freitag C, Tauber R, Mossner R, Franke P, and others. 2004. Association of a functional-1019C>G 5-HT1A receptor gene polymorphism with panic disorder with agoraphobia. Int J Neuropsychopharmacol7:1-4.
123.
Rotondo A, Nielsen DA, Nakhai B, Hulihan-Giblin B, Bolos A, Goldman D.1997. Agonist-promoted down-regulation and functional desensitization in two naturally occurring variants of the human serotonin1A receptor. Neuropsychopharmacology17:18-26.
124.
Rumajogee P, Madeira A, Verge D, Hamon M, Miquel M-C.2002. Up-regulation of the neuronal serotoninergic phenotype in vitro: BDNF and cAMP share Trk B-dependent mechanisms. J Neurochem83:1525-1528.
125.
Rumajogee P, Verge D, Hanoun N, Brisorgueil MJ, Hen R, Lesch KP, and others. 2004. Adaption of the serotoninergic neuronal pheno-type in the absence of 5-HT autoreceptors or the 5-HT transporter: involvement of BDNF and cAMP. Eur J Neurosci19:937-944.
126.
Rupniak NM, Kramer MS. 1999. Discovery of the antidepressant and anti-emetic efficacy of substance P receptor (NK1) antagonists. Trends Pharmacol Sci20:485-490.
127.
Saarelainen T, Hendolin P, Lucas G, Koponen E, Sairanen M, MacDonald E, and others. 2003. Activation of the TrkB neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant-induced behavioral effects. J Neurosci23:349-357.
128.
Sakai K, Nakamura M, Ueno S, Sano A, Sakai N, Shirai Y, and others. 2002. The silencer activity of the novel human serotonin transporter linked polymorphic regions. Neurosci Lett327:13-16.
129.
Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, and others. 2003. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science301:805-809.
130.
Santarelli N, Gross C, Monckton J, Dulawa S, Lee J, Saxe M, and others. 2001. The 5-HT1A receptor is required for the effect of chronic fluoxetine on behavior and neurogenesis. Proc Soc Neurosci27:858-14.
131.
Sargent PA, Kjaer KH, Bench CJ, Rabiner EA, Messa C, Meyer J, and others. 2000. Brain serotonin1A receptor binding measured by positron emission tomography with [11C]WAY-100635: effects of depression and antidepressant treatment. Arch Gen Psychiatry57:174-180.
132.
Sarnyai Z, Sibille EL, Pavlides C, Fenster RJ, McEwen BS, Toth M.2000. Impaired hippocampal-dependent learning and functional abnormalities in the hippocampus in mice lacking serotonin1A receptors. Proc Natl Acad Sci U S A97:14731-14736.
133.
Schechter MD, Chance WT. 1979. Non-specificity of “behavioral despair” as an animal model of depression. Eur J Pharmacol60:139-142.
134.
Schoenherr CJ, Anderson DJ. 1995. The neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuron-specific genes. Science267:1360-1363.
135.
Schramm NL, McDonald MP, Limbird LE. 2001. The alpha(2a)adrenergic receptor plays a protective role in mouse behavioral models of depression and anxiety. J Neurosci21:4875-4882.
136.
Segurado R, Detera-Wadleigh SD, Levinson DF, Lewis CM, Gill M, Nurnberger JI Jr, and others. 2003. Genome scan meta-analysis of schizophrenia and bipolar disorder, part III: bipolar disorder. Am J Hum Genet73:49-62.
137.
Shen C, Li H, Meller E.2002. Repeated treatment with antidepressants differentially alters 5-HT1A agonist-stimulated [35S]GTP gamma S binding in rat brain regions. Neuropharmacology42:1031-1038.
138.
Shenoy SK, Lefkowitz RJ. 2003. Multifaceted roles of beta-arrestins in the regulation of seven-membrane-spanning receptor trafficking and signalling. Biochem J375:503-515.
139.
Shioe K, Ichimiya T, Suhara T, Takano A, Sudo Y, Yasuno F, and others. 2003. No association between genotype of the promoter region of serotonin transporter gene and serotonin transporter binding in human brain measured by PET. Synapse48:184-188.
140.
Sotelo C, Cholley B, El Mestikawy S. EM, Gozlan H, Hamon M.1990. Direct immunohistochemical evidence of the existence of 5-HT1A autoreceptors on serotoninergic neurons in the midbrain raphe nuclei. Eur J Neurosci2:1144-1154.
141.
Stahl SM. 1998. Mechanism of action of serotonin selective reuptake inhibitors. Serotonin receptors and pathways mediate therapeutic effects and side effects. J Affect Disord51:215-235.
142.
Stephens JC, Schneider JA, Tanguay DA, Choi J, Acharya T, Stanley SE, and others. 2001. Haplotype variation and linkage disequilibrium in 313 human genes. Science293:489-493.
143.
Stockmeier CA, Shapiro LA, Dilley GE, Kolli TN, Friedman L, Rajkowska G.1998. Increase in serotonin-1A autoreceptors in the midbrain of suicide victims with major depression-postmortem evidence for decreased serotonin activity. J Neurosci18:7394-7401.
144.
Storring JM, Charest A, Cheng P, Albert PR. 1999. TATA-driven transcriptional initiation and regulation of the rat serotonin 5-HT1A receptor gene. J Neurochem72:2238-2247.
145.
Strobel A, Gutknecht L, Rothe C, Reif A, Mossner R, Zeng Y, and others. 2003. Allelic variation in 5-HT(1A) receptor expression is associated with anxiety-and depression-related personality traits. J Neural Transm110:1445-1453.
146.
Sumiyoshi T, Stockmeier CA, Overholser JC, Dilley GE, Meltzer HY. 1996. Serotonin1A receptors are increased in postmortem pre-frontal cortex in schizophrenia. Brain Res708:209-214.
147.
Tauscher J, Kapur S, Verhoeff NP, Hussey DF, Daskalakis ZJ, Tauscher-Wisniewski S, and others. 2002. Brain serotonin 5-HT(1A) receptor binding in schizophrenia measured by positron emission tomography and [11C]WAY-100635. Arch Gen Psychiatry59:514-520.
148.
Törk I. 1990. Anatomy of the serotonergic system. Ann N Y Acad Sci600:9-34; discussion 34-35.
149.
Underwood MD, Khaibulina AA, Ellis SP, Moran A, Rice PM, Mann JJ, and others. 1999. Morphometry of the dorsal raphe nucleus serotonergic neurons in suicide victims. BiolPsychiatry46:473-483.
150.
Vazquez DM, Lopez JF, Van Hoers H, Watson SJ, Levine S.2000. Maternal deprivation regulates serotonin 1A and 2A receptors in the infant rat. Brain Res855:76-82.
151.
Vazquez DM, Van Oers H, Levine S, Akil H.1996. Regulation of glucocorticoid and mineralocorticoid receptor mRNAs in the hippocampus of the maternally deprived infant rat. Brain Res731:79-90.
152.
Veenstra-VanderWeele J, Anderson GM, Cook EH Jr.2000. Pharmacogenetics and the serotonin system: initial studies and future directions. Eur J Pharmacol410:165-181.
153.
Vreugdenhil E, de Kloet ER, Schaaf M, Datson NA. 2001. Genetic dissection of corticosterone receptor function in the rat hippocampus. Eur Neuropsychopharmacol11:423-430.
154.
Walther DJ, Peter JU, Bashammakh S, Hortnagl H, Voits M, Fink H, and others. 2003. Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science299:76.
155.
Weaver IC, La Plante P, Weaver S, Parent A, Sharma S, Diorio J, and others. 2001. Early environmental regulation of hippocampal glucocorticoid receptor gene expression: characterization of intracellular mediators and potential genomic target sites. Mol Cell Endocrinol185:205-218.
156.
White LA, Eaton MJ, Castro MC, Klose KJ, Globus MY, Shaw G, and others. 1994. Distinct regulatory pathways control neurofilament expression and neurotransmitter synthesis in immortalized serotonergic neurons. J Neurosci14:6744-6753.
157.
Wilson CC, Faber KM, Haring JH. 1998. Serotonin regulates synaptic connections in the dentate molecular layer of adult rats via 5-HT1a receptors: evidence for a glial mechanism. Brain Res782:235-239.
158.
Wissink S, Meijer O, Pearce D, van Der Burg B, van Der Saag PT. 2000. Regulation of the rat serotonin-1A receptor gene by corticosteroids. J Biol Chem275:1321-1326.
159.
World Health Organization. 2001. The world health report 2001. Mental health, new understanding, new hope. Geneva, Switzerland: WHO Marketing and Dissemination.
160.
Wu S, Comings DE. 1999. A common C-1018G polymorphism in the human 5-HT1A receptor gene. Psychiatr Genet9:105-106.
161.
Yan W, Wilson CC, Haring JH. 1997. Effects of neonatal serotonin depletion on the development of rat dentate granule cells. Brain Res Dev Brain Res98:177-184.
162.
Young SN. 1993. The use of diet and dietary components in the study of factors controlling affect in humans: a review. J Psychiatry Neurosci18:235-244.
163.
Yu F, Thiesen J, Stratling WH. 2000. Histone deacetylase-independent transcriptional repression by methyl-CpG-binding protein 2. Nucleic Acids Res28:2201-2206.
164.
Zanardi R, Serretti A, Rossini D, Franchini L, Cusin C, Lattuada E, and others. 2001. Factors affecting fluvoxamine antidepressant activity: influence of pindolol and 5-HTTLPR in delusional and nondelusional depression. Biol Psychiatry50:323-330.
165.
Zhong P, Ciaranello RD. 1995. Transcriptional regulation of hippocampal 5-HT1a receptors by corticosteroid hormones. Brain Res Mol Brain Res29:23-34.
