Slc6a4

Summary

Gene Symbol: Slc6a4
Description: solute carrier family 6 (neurotransmitter transporter), member 4
Alias: 5HT transporter, 5HTT, Solute carrier family 6 (neurotransmitter transporter serotonin) member 4 (5-hydroxytryptamine (serotonin) transporter), serotonin transporter, sodium-dependent serotonin transporter, solute carrier family 6 (neurotransmitter transporter serotonin) member 4 (5-hydroxytryptamine (serotonin) transporter), solute carrier family 6 (neurotransmitter transporter, serotonin), member 4, solute carrier family 6, member 4
Species: rat

Top Publications

  1. doi A study in male and female 5-HT transporter knockout rats: an animal model for anxiety and depression disorders
    J D A Olivier
    Department of Cognitive Neuroscience Psychoneuropharmacology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
    Neuroscience 152:573-84. 2008
  2. pmc Functional genetic variants that increase synaptic serotonin and 5-HT3 receptor sensitivity predict alcohol and drug dependence
    M A Enoch
    Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892, USA
    Mol Psychiatry 16:1139-46. 2011
  3. doi In vivo effects of a combined 5-HT1B receptor/SERT antagonist in experimental pulmonary hypertension
    Ian Morecroft
    FBLS, University of Glasgow, Glasgow G12 8QQ, UK
    Cardiovasc Res 85:593-603. 2010
  4. ncbi Regulating the conducting states of a mammalian serotonin transporter
    Michael W Quick
    Department of Biological Sciences, 3641 Watt Way, HNB 228, University of Southern California, Los Angeles, CA 90089, USA
    Neuron 40:537-49. 2003
  5. doi Adaptations in pre- and postsynaptic 5-HT1A receptor function and cocaine supersensitivity in serotonin transporter knockout rats
    Judith R Homberg
    Hubrecht Institute, Uppsalalaan 8, 3584, CT, Utrecht, The Netherlands
    Psychopharmacology (Berl) 200:367-80. 2008
  6. ncbi Deficiency of the 5-hydroxytryptamine transporter gene leads to cardiac fibrosis and valvulopathy in mice
    A Mekontso-Dessap
    Institut National de la Santé et de la Recherche Médicale INSERM Unité 651, Departement de Physiologie, Universite Paris XII, CHU Henri Mondor, Assistance Publique Hopitaux de Paris, Creteil, France
    Circulation 113:81-9. 2006
  7. ncbi Serotonin (5-HT) transporter (SERT) function after graded destruction of serotonergic neurons
    Sylvia Montañez
    Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229 3900, USA
    J Neurochem 87:861-7. 2003
  8. ncbi Potentiation of 5-hydroxytryptamine (5-HT) responses by a 5-HT uptake inhibitor in pulmonary and systemic vessels: effects of exposing rats to hypoxia
    Janet C Wanstall
    School of Biomedical Sciences, Department of Physiology and Pharmacology, The University of Queensland, St Lucia, 4072 Brisbane, Queensland, Australia
    Naunyn Schmiedebergs Arch Pharmacol 368:520-7. 2003
  9. ncbi Raloxifene blocks estradiol induction of the serotonin transporter and 5-hydroxytryptamine2A receptor in female rat brain
    B E H Sumner
    MRC Brain Metabolism Unit, University Department of Neuroscience, 1 George Square, Edinburgh EH8 9JZ, UK
    Neurosci Lett 417:95-9. 2007
  10. doi Development of 5-HT(1B), SERT and thalamo-cortical afferents in early nutrionally restricted rats: an emerging explanation for delayed barrel formation
    Ivett Medina-Aguirre
    Laboratorio de Patología Molecular, Unidad de Investigación Biomolecular en Cardiología, Hospital de Cardiologia, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico 06725, DF, Mexico
    Int J Dev Neurosci 26:225-31. 2008

Research Grants

  1. Dopamine D4 Receptor in Sustained Attention
    Kehong Zhang; Fiscal Year: 2003
  2. Gene-Gene Interactions in Pulmonary Hypertension
    ELISABETH WILLERS; Fiscal Year: 2006
  3. Arterial 5-HT Transporter Function
    Stephanie Watts; Fiscal Year: 2007
  4. Arterial 5-HT Transporter Function
    Stephanie Watts; Fiscal Year: 2009
  5. Computational and Biochemical Docking of Dopamine Transporter Antagonists
    Roxanne A Vaughan; Fiscal Year: 2010

Scientific Experts

Detail Information

Publications81

  1. doi A study in male and female 5-HT transporter knockout rats: an animal model for anxiety and depression disorders
    J D A Olivier
    Department of Cognitive Neuroscience Psychoneuropharmacology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
    Neuroscience 152:573-84. 2008
    ..This knockout rat model may provide a valuable model to study anxiety- and depression-related disorders in male and female rats...
  2. pmc Functional genetic variants that increase synaptic serotonin and 5-HT3 receptor sensitivity predict alcohol and drug dependence
    M A Enoch
    Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892, USA
    Mol Psychiatry 16:1139-46. 2011
    ..male controls were genotyped for the triallelic 5-HTTLPR functional polymorphism in the 5-HT transporter gene (SLC6A4) and 16 haplotype-tagging single-nucleotide polymorphisms (SNPs) across HTR3B (including the functional rs1176744 ..
  3. doi In vivo effects of a combined 5-HT1B receptor/SERT antagonist in experimental pulmonary hypertension
    Ian Morecroft
    FBLS, University of Glasgow, Glasgow G12 8QQ, UK
    Cardiovasc Res 85:593-603. 2010
    ..Here we determine, for the first time, the in vivo effects of a combined 5-HT1B receptor/serotonin transporter antagonist (LY393558) with respect to the development of pulmonary arterial hypertension (PAH) and its in ..
  4. ncbi Regulating the conducting states of a mammalian serotonin transporter
    Michael W Quick
    Department of Biological Sciences, 3641 Watt Way, HNB 228, University of Southern California, Los Angeles, CA 90089, USA
    Neuron 40:537-49. 2003
    ..These data show that protein interactions govern SERT activity and suggest that both cell excitability and psychostimulant-mediated effects will be dependent upon the state of association among SERT and its interacting partners...
  5. doi Adaptations in pre- and postsynaptic 5-HT1A receptor function and cocaine supersensitivity in serotonin transporter knockout rats
    Judith R Homberg
    Hubrecht Institute, Uppsalalaan 8, 3584, CT, Utrecht, The Netherlands
    Psychopharmacology (Berl) 200:367-80. 2008
    ..While individual differences in vulnerability to psychostimulants have been largely attributed to dopaminergic neurotransmission, the role of serotonin is not fully understood...
  6. ncbi Deficiency of the 5-hydroxytryptamine transporter gene leads to cardiac fibrosis and valvulopathy in mice
    A Mekontso-Dessap
    Institut National de la Santé et de la Recherche Médicale INSERM Unité 651, Departement de Physiologie, Universite Paris XII, CHU Henri Mondor, Assistance Publique Hopitaux de Paris, Creteil, France
    Circulation 113:81-9. 2006
    ..Here we investigated whether 5-HTT-deficient (5-HTT-KO) mice developed structural and/or functional cardiac abnormalities and valvulopathy...
  7. ncbi Serotonin (5-HT) transporter (SERT) function after graded destruction of serotonergic neurons
    Sylvia Montañez
    Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229 3900, USA
    J Neurochem 87:861-7. 2003
    The degree of occupancy of the serotonin transporter (SERT) by selective serotonin reuptake inhibitors (SSRIs) appears to be critical in determining therapeutic response...
  8. ncbi Potentiation of 5-hydroxytryptamine (5-HT) responses by a 5-HT uptake inhibitor in pulmonary and systemic vessels: effects of exposing rats to hypoxia
    Janet C Wanstall
    School of Biomedical Sciences, Department of Physiology and Pharmacology, The University of Queensland, St Lucia, 4072 Brisbane, Queensland, Australia
    Naunyn Schmiedebergs Arch Pharmacol 368:520-7. 2003
    ..The findings may have implications in relation to the suggested use of SERT inhibitors in the treatment of pulmonary hypertension...
  9. ncbi Raloxifene blocks estradiol induction of the serotonin transporter and 5-hydroxytryptamine2A receptor in female rat brain
    B E H Sumner
    MRC Brain Metabolism Unit, University Department of Neuroscience, 1 George Square, Edinburgh EH8 9JZ, UK
    Neurosci Lett 417:95-9. 2007
    ..female rat induces expression of the genes for the 5-hydroxytryptamine(2A) receptor (5-HT(2A)R) and the serotonin transporter (SERT) in the dorsal raphe nucleus (DRN)...
  10. doi Development of 5-HT(1B), SERT and thalamo-cortical afferents in early nutrionally restricted rats: an emerging explanation for delayed barrel formation
    Ivett Medina-Aguirre
    Laboratorio de Patología Molecular, Unidad de Investigación Biomolecular en Cardiología, Hospital de Cardiologia, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico 06725, DF, Mexico
    Int J Dev Neurosci 26:225-31. 2008
    ..We then evaluated the pattern of immunostaining of the serotonin transporter (SERT) and of the serotonin receptor 1B (5-HT(1B)), as well as the growth and arrival time of ..
  11. ncbi 13-cis-Retinoic acid alters intracellular serotonin, increases 5-HT1A receptor, and serotonin reuptake transporter levels in vitro
    Kally C O'Reilly
    Institute of Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas 78712, USA
    Exp Biol Med (Maywood) 232:1195-203. 2007
    ..Increases in both 5-HT(1A) receptor and SERT proteins may lead to decreased serotonin availability at synapses. Such an effect of 13-cis-RA could contribute to the increased depression-related behaviors we have shown in mice...
  12. doi Vascular reactivity, 5-HT uptake, and blood pressure in the serotonin transporter knockout rat
    A Elizabeth Linder
    Dept of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824 1317, USA
    Am J Physiol Heart Circ Physiol 294:H1745-52. 2008
    The handling of serotonin [5-hydroxytryptamine (5-HT)] depends on the serotonin transporter (SERT)...
  13. pmc The existence of a local 5-hydroxytryptaminergic system in peripheral arteries
    W Ni
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824 1317, USA
    Br J Pharmacol 154:663-74. 2008
    ..We hypothesized that a local 5-hydroxytryptaminergic system (including 5-HT synthesis, metabolism, uptake and release) with physiological function exists in peripheral arteries...
  14. ncbi Dexfenfluramine-associated changes in 5-hydroxytryptamine transporter expression and development of hypoxic pulmonary hypertension in rats
    S Eddahibi
    INSERM U492, Departement de Physiologie, Faculté de Médecine de Créteil, Hôpital H Mondor, 94010 Creteil, France
    J Pharmacol Exp Ther 297:148-54. 2001
    ..01) than in rats pretreated with the vehicle. These data show that, in rats, the increased 5-HTT expression that follows dexfenfluramine discontinuation promotes the development of hypoxic pulmonary hypertension...
  15. ncbi Regulation of the serotonin transporter by interacting proteins
    J Haase
    Biochemistry Department, Trinity College, Dublin 2, Ireland
    Biochem Soc Trans 29:722-8. 2001
    The serotonin transporter (SERT) plays a critical role in the maintenance of normal neurotransmission by serotonin [5-hydroxytryptamine (5-HT)]...
  16. ncbi Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype
    N Ozaki
    Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
    Mol Psychiatry 8:933-6. 2003
    Two common serotonin transporter (SERT) untranslated region gene variants have been intensively studied, but remain inconclusively linked to depression and other neuropsychiatric disorders...
  17. ncbi Subcellular redistribution of the serotonin transporter by secretory carrier membrane protein 2
    Heidi Kaastrup Müller
    School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin 4, Ireland, Trinity College Dublin 2, Ireland
    J Biol Chem 281:28901-9. 2006
    The serotonin transporter (SERT) belongs to the SLC6 family of sodium- and chloride-dependent neurotransmitter transporters responsible for uptake of amino acids and biogenic amines from extracellular spaces...
  18. ncbi Phosphorylation of threonine residue 276 is required for acute regulation of serotonin transporter by cyclic GMP
    Sammanda Ramamoorthy
    Department of Neurosciences, Division of Neuroscience Research, Medical University of South Carolina, Charleston, South Carolina 29425
    J Biol Chem 282:11639-47. 2007
    Cellular protein kinases, phosphatases, and other serotonin transporter (SERT) interacting proteins participate in several signaling mechanisms regulating SERT activity...
  19. ncbi Partitioning of the serotonin transporter into lipid microdomains modulates transport of serotonin
    Francesca Magnani
    Department of Biochemistry, Trinity College, Dublin 2, Ireland
    J Biol Chem 279:38770-8. 2004
    The serotonin transporter (SERT) is an integral membrane protein responsible for the clearance of serotonin from the synaptic cleft following the release of the neurotransmitter...
  20. ncbi The cytoplasmic substrate permeation pathway of serotonin transporter
    Yuan Wei Zhang
    Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520 8066, USA
    J Biol Chem 281:36213-20. 2006
    b>Serotonin transporter (SERT) catalyzes reuptake of the neurotransmitter serotonin (5-HT) and is a target for antidepressant drugs and psychostimulants. It is a member of a large family of neurotransmitter and amino acid transporters...
  21. ncbi A role for p38 mitogen-activated protein kinase in the regulation of the serotonin transporter: evidence for distinct cellular mechanisms involved in transporter surface expression
    Devadoss J Samuvel
    Department of Physiology and Neuroscience, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    J Neurosci 25:29-41. 2005
    The serotonin transporter (SERT) is regulated by various signaling mechanisms that may operate to maintain appropriate levels of synaptic serotonin (5-HT)...
  22. pmc Peripuberty stress leads to abnormal aggression, altered amygdala and orbitofrontal reactivity and increased prefrontal MAOA gene expression
    C Marquez
    Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Federale de Lausanne EPFL, Lausanne, Switzerland
    Transl Psychiatry 3:e216. 2013
    ..Our data emphasize the impact of biological factors triggered by peripubertal adverse experiences on the emergence of violent behaviors...
  23. doi Amelioration of hypoxia-induced striatal 5-HT(2A) receptor, 5-HT transporter and HIF1 alterations by glucose, oxygen and epinephrine in neonatal rats
    T R Anju
    Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin 682022, Kerala, India
    Neurosci Lett 502:129-32. 2011
    ..5HT(2A) receptor number was increased in hypoxic neonates along with an up regulation of 5HT(2A) receptor and 5HT transporter gene. The enhanced striatal 5HT(2A) receptors modulate the ventilatory response to hypoxia...
  24. doi Association between polymorphisms in serotonin and dopamine-related genes and endogenous pain modulation
    Roi Treister
    The Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel
    J Pain 12:875-83. 2011
    ..variable number of tandem repeat (VNTR) polymorphisms of the following candidate genes were studied: 1) serotonin transporter (5-HTTLPR); 2) dopamine transporter (DAT1); 3) dopamine receptor 4 (DRD4); and 4) monoamine oxidase A (..
  25. doi Serotonin transporter knockout rats show improved strategy set-shifting and reduced latent inhibition
    Lourens J P Nonkes
    Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, Department of Cognitive Neuroscience, Radboud University Nijmegen Medical Centre, 6525 EZ, The Netherlands
    Learn Mem 19:190-3. 2012
    ..b>Serotonin transporter knockout (5-HTT(-/-)) rodents show improved reversal learning in addition to orbitofrontal cortex changes...
  26. ncbi Serotonin transporter binding increases in caudate-putamen and nucleus accumbens after neonatal 6-hydroxydopamine lesions in rats: implications for motor hyperactivity
    Kehong Zhang
    Mailman Research Center, McLean Division of Massachusetts General Hospital, 115 Mill Street, Belmont, MA 02478, USA
    Brain Res Dev Brain Res 137:135-8. 2002
    ..These findings suggest that excess 5-HT transporters reflect serotonin hyperinnervation reported to occur in lesioned rats, and may modulate motor hyperactivity...
  27. doi 5HTT genotype moderates the influence of early institutional deprivation on emotional problems in adolescence: evidence from the English and Romanian Adoptee (ERA) study
    Robert Kumsta
    MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King s College London, UK
    J Child Psychol Psychiatry 51:755-62. 2010
    A common polymorphism in the serotonin transporter gene (SLC6A4, 5HTT) has been repeatedly shown to moderate the influence of childhood adversity and stressful life events on the development of psychopathology...
  28. pmc Adverse early life experience and social stress during adulthood interact to increase serotonin transporter mRNA expression
    Katherine L Gardner
    Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, UK
    Brain Res 1305:47-63. 2009
    ..life experience, adverse experiences during adulthood, and potential interactions between these factors on serotonin transporter (slc6a4) mRNA expression, we investigated in rats the effects of maternal separation (180 min/day from ..
  29. doi Serotonin transporter deficiency in rats contributes to impaired object memory
    J D A Olivier
    Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Molecular Neurobiology and Psychoneuropharmacology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Genes Brain Behav 8:829-34. 2009
    Serotonin is well known for its role in affection, but less known for its role in cognition. The serotonin transporter (SERT) has an essential role in serotonergic neurotransmission as it determines the magnitude and duration of the ..
  30. doi Genetic polymorphisms of the serotonin transporter, but not the 2a receptor or nitric oxide synthetase, are associated with pulmonary hypertension in chronic obstructive pulmonary disease
    Silvia Ulrich
    Clinics of Internal Medicine and Pulmonology, University Hospital Zurich, Zurich, Switzerland
    Respiration 79:288-95. 2010
    ..Pulmonary hypertension (PH) is prognosti- cally important in chronic obstructive pulmonary disease (COPD). Since PH only weakly correlates with hypoxemia, other factors must play a role...
  31. doi Continuous fluoxetine administration prevents recurrence of pulmonary arterial hypertension and prolongs survival in rats
    Shao Ping Zhu
    Department of Cardiothoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China
    Clin Exp Pharmacol Physiol 36:e1-5. 2009
    1. The serotonin transporter (SERT) is strongly implicated in the pathogenesis of pulmonary arterial hypertension (PAH) in patients and animal models...
  32. doi Serotonin transporter deficiency increases abdominal fat in female, but not male rats
    Judith R Homberg
    Functional Genomics and Bioinformatics, Hubrecht Institute, University Medical Center Utrecht, Utrecht, The Netherlands
    Obesity (Silver Spring) 18:137-45. 2010
    ..The underlying mechanisms are poorly understood. We found that female, but not male, depression-prone serotonin transporter knockout (SERT(-/-)) rats had a strong increase (54%) in abdominal fat, whereas no increases in plasma ..
  33. doi Deletion of the serotonin transporter in rats disturbs serotonin homeostasis without impairing liver regeneration
    Ramadhan B Matondo
    Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3508 TD Utrecht, The Netherlands
    Am J Physiol Gastrointest Liver Physiol 296:G963-8. 2009
    The serotonin transporter is implicated in the uptake of the vasoconstrictor serotonin from the circulation into the platelets, where 95% of all blood serotonin is stored and released in response to vascular injury...
  34. doi Chronic buspirone treatment decreases 5-HT1B receptor densities and the serotonin transporter but increases the density of 5-HT2A receptors in the bulbectomized rat model of depression: an autoradiographic study
    Hiroki Sato
    Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
    Brain Res 1345:28-44. 2010
    ..The results indicate differential effects of chronic antidepressant treatment on the 5-HT system regulation in the OBX model of depression and normal rats...
  35. pmc Association study of serotonin transporter gene polymorphisms with obstructive sleep apnea syndrome in Chinese Han population
    Weihua Yue
    Mental Health Institute, The Second Xiangya Hospital, Central South University, Changsha, PR China
    Sleep 31:1535-41. 2008
    Since the serotonin (5-HT) is associated with circadian rhythm and breathing regulation, the serotonin transporter (5-HTT), which plays an important role in serotoninergic transmission, might be a strong candidate gene in the ..
  36. doi Chronic effect of nicotine on serotonin transporter mRNA in the raphe nucleus of rats: reversal by co-administration of bupropion
    Jun ichi Semba
    Division of Health Sciences, The Open University of Japan, Chiba, Japan
    Psychiatry Clin Neurosci 62:435-41. 2008
    ..during smoking cessation, an animal model of nicotine withdrawal was used, and the expression of serotonin transporter (5HTT), abnormality of which is implicated in the pathogenesis of depression, was investigated...
  37. doi [Association of 5-hydroxytryptamine transporter gene polymorphism with asthma and comorbid depression]
    Lan Wang
    Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, PR China
    Zhonghua Yi Xue Yi Chuan Xue Za Zhi 26:575-9. 2009
    ..To explore the molecular genetic mechanism of complicating depression in asthma by detecting two gene polymorphisms of 5-hydroxytryptamine transporter (5-HTTLPR/Stin2) gene...
  38. doi Association study of serotonin transporter gene polymorphisms and ventricular septal defects related possible pulmonary arterial hypertension in Chinese population
    Hailong Cao
    Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
    Clin Exp Hypertens 31:605-14. 2009
    Polymorphisms of serotonin transporter (5-HTT) gene were hypothesized to be associated with ventricular septal defects (VSD) related ultrasonographic pulmonary arterial hypertension (PAH) susceptibility...
  39. ncbi Isolation of cDNAs encoding a novel member of the neurotransmitter transporter gene family
    W Mayser
    Abteilung Neurochemie, Max Planck Institut für Hirnforschung, Frankfurt, Germany
    FEBS Lett 295:203-6. 1991
    ..PCR amplification revealed low-level expression of NTT transcripts in spinal cord, but not in brain and cerebellum...
  40. pmc A conserved asparagine residue in transmembrane segment 1 (TM1) of serotonin transporter dictates chloride-coupled neurotransmitter transport
    L Keith Henry
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 8548, USA
    J Biol Chem 286:30823-36. 2011
    ..and Cl(-)-dependent uptake of neurotransmitters via transporters of the SLC6 family, including the human serotonin transporter (SLC6A4), is critical for efficient synaptic transmission...
  41. doi Serotonin transporter genotype x construction stress interaction in rats
    Pieter Schipper
    Department of Anatomy, Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Behav Brain Res 223:169-75. 2011
    ..x environment interactions in psychiatry is the one involving the low activity (s) allelic variant of the serotonin transporter (5-HTT) promoter polymorphism (5-HTTLPR) that in the context of stress increases risk for depression...
  42. pmc In vivo studies of the SERT-selective [18F]FPBM and VMAT2-selective [18F]AV-133 radiotracers in a rat model of Parkinson's disease
    Julie L Wang
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Nucl Med Biol 37:479-86. 2010
    ..2-(2'-((dimethylamino)methyl)-4'-(3-[(18)F]-fluoropropoxy)phenylthio)benzenamine], a selective serotonin transporter (SERT) tracer, and [(18)F]AV-133 [(+)-2-Hydroxy-3-isobutyl-9-(3-fluoropropoxy)-10-methoxy-1,2,3,4,6,7-..
  43. doi Orbitofrontal cortex and amygdalar over-activity is associated with an inability to use the value of expected outcomes to guide behaviour in serotonin transporter knockout rats
    Lourens J P Nonkes
    Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, Dept of Cognitive Neuroscience, Radboud University Nijmegen Medical Centre, Geert Grooteplein 21, 6525 GA Nijmegen, The Netherlands
    Neurobiol Learn Mem 94:65-72. 2010
    ..5-HT levels are tightly controlled by the serotonin transporter (5-HTT). We and others have observed that 5-HTT availability affects reversal learning...
  44. ncbi Role of C-terminal region in the functional regulation of rat serotonin transporter (SERT)
    Hideki Mochizuki
    Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Hiroshima University, 1 2 3 Kasumi Minami ku, Hiroshima 734 8551, Japan
    Neurochem Int 46:93-105. 2005
    Previously, we revealed that the state of the actin cytoskeleton affects the uptake activity of the serotonin transporter (SERT)...
  45. pmc Postnatal changes in tryptophan hydroxylase and serotonin transporter immunoreactivity in multiple brainstem nuclei of the rat: implications for a sensitive period
    Qiuli Liu
    Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    J Comp Neurol 518:1082-97. 2010
    ..we conducted a large-scale investigation of the 5-HT-synthesizing enzyme tryptophan hydroxylase (TPH) and serotonin transporter (SERT) with semiquantitative immunohistochemistry in multiple brainstem nuclei of normal rats aged P2-21...
  46. doi Reduced function of the serotonin transporter is associated with decreased expression of BDNF in rodents as well as in humans
    Raffaella Molteni
    Center of Neuropharmacology, Department of Pharmacological Sciences, Universita degli Studi di Milano, Milan, Italy
    Neurobiol Dis 37:747-55. 2010
    ..identify the molecular mechanisms that may contribute to the enhanced susceptibility to depression under serotonin transporter (SERT) dysfunction, we analyzed the expression of brain-derived neurotrophic factor (BDNF), a key player ..
  47. doi Effects of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin transporter and vesicular monoamine transporter 2 protein and gene expression in rats: implications for MDMA neurotoxicity
    Dominik K Biezonski
    Neuroscience and Behavior Program, University of Massachusetts, Amherst, Massachusetts, USA
    J Neurochem 112:951-62. 2010
    ..Experiment 1 investigated MDMA-induced changes in levels of the serotonin transporter (SERT) and the vesicular monoamine transporter 2 (VMAT-2) in the hippocampus, a region with sparse ..
  48. doi Changes in NPY and POMC, but not serotonin transporter, following a restricted feeding/repletion protocol in rats
    Nuria Lauzurica
    Unidad de Cartografía Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, 28040 Madrid, Spain
    Brain Res 1313:103-12. 2010
    ..Food-restricted animals provide a tool for the further study of neurochemical alterations and for the development of new drugs to treat alterations that may occur in humans when dieting is abandoned...
  49. ncbi Immunohistochemical study of the serotonergic neuronal system in an animal model of the mood disorder
    Shuji Iritani
    Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466 8550, Japan
    Exp Neurol 201:60-5. 2006
    ..examined vesicle monoamine transporter 2 (VMAT2), serotonin receptor type 1a (5HT1a), and serotonin transporter (5HTT) in the hippocampal region of reserpine-treated rats, an animal model of depression...
  50. pmc Lack of the serotonin transporter does not prevent mineralocorticoid hypertension in rat and mouse
    Wei Ni
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824 1317, USA
    Eur J Pharmacol 589:225-7. 2008
    We hypothesized that lack of a functional serotonin transporter (SERT) would increase basal blood pressure and enhance the development of deoxycorticosterone acetate (DOCA)-salt hypertension compared to wild type (WT) controls...
  51. pmc Serotonin transporter polymorphisms in familial and idiopathic pulmonary arterial hypertension
    Elisabeth D Willers
    Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Medical Center North T 1218, Nashville, TN 37232 2650, USA
    Am J Respir Crit Care Med 173:798-802. 2006
    Serotonin is a pulmonary vasoconstrictor and smooth muscle cell mitogen. The serotonin transporter (SERT) is abundant in pulmonary vascular smooth muscle...
  52. ncbi Cysteine-scanning mutagenesis of the fifth external loop of serotonin transporter
    Preston C Keller
    Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520 8066, USA
    Biochemistry 43:8510-6. 2004
    External loop 5 (EL5) of serotonin transporter was analyzed by mutating each of the residues from Thr-480 to Ala-511, one at a time, with cysteine...
  53. ncbi Repeat length polymorphism of the serotonin transporter gene influences pulmonary artery pressure in heart failure
    Thomas P Olson
    Mayo Clinic, College of Medicine, Rochester, MN 55905, USA
    Am Heart J 153:426-32. 2007
    ..Polymorphisms of the serotonin transporter (5-HTT) gene have been implicated in contributing to smooth muscle dysfunction and remodeling of the ..
  54. ncbi Depressive behaviors and decreased expression of serotonin reuptake transporter in rats that experienced neonatal maternal separation
    Jong Ho Lee
    Dental Research Institute, Department of Oral and Maxillofacial Surgery, Seoul National University School of Dentistry, Seoul 110 744, Republic of Korea
    Neurosci Res 58:32-9. 2007
    ..These results suggest that neonatal maternal separation may result in the development of depression- and/or anxiety-like behaviors in later life, in which the long-term alterations in 5-HTergic neurotransmission may take a role...
  55. ncbi Neurochemical characterization of pathways expressing plasma membrane monoamine transporter in the rat brain
    V Vialou
    INSERM, U513, Faculte de Medecine, Creteil, F 94010 France Université Paris XII, Creteil, France
    Neuroscience 144:616-22. 2007
    ..Taken together, our observations support a role for PMAT in monoamine uptake in cholinergic neurons...
  56. ncbi The serotonin transporter and 5HT2A receptor in rat brain after localized lesions
    Henrik Dam
    Department of Psychiatry, H S Rigshospitalet, Copenhagen, Denmark
    Neurol Res 29:717-22. 2007
    ..The purpose of the present study was to examine whether serotonin transporter density or 5HT2A serotonin receptor density is changed in specific brain areas following anterior or ..
  57. ncbi Three autism candidate genes: a synthesis of human genetic analysis with other disciplines
    Christopher W Bartlett
    Center for Statistical Genetics Research, University of Iowa, Iowa City, IA, USA
    Int J Dev Neurosci 23:221-34. 2005
    ..From this body of work we highlight results from three candidate genes, REELIN (RELN), SEROTONIN TRANSPORTER (5HTT), and ENGRAILED 2 (EN2) and discuss the relevant neuroscience, molecular genetics, and statistical ..
  58. ncbi Cysteine-scanning mutagenesis of serotonin transporter intracellular loop 2 suggests an alpha-helical conformation
    Yuan Wei Zhang
    Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520 8066, USA
    J Biol Chem 280:30807-13. 2005
    Like other proteins involved in neurotransmitter transport, serotonin transporter (SERT) activity is regulated by multiple intracellular signal transduction pathways...
  59. ncbi Loss of serotonin transporter protein after MDMA and other ring-substituted amphetamines
    Tao Xie
    Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA
    Neuropsychopharmacology 31:2639-51. 2006
    We studied in vivo expression of the serotonin transporter (SERT) protein after 3,4-methylenedioxymethamphetamine (MDMA), p-chloroamphetamine (PCA), or fenfluramine (FEN) treatments, and compared the effects of substituted amphetamines ..
  60. ncbi Genetic association of the serotonin transporter in pulmonary arterial hypertension
    Rajiv D Machado
    Division of Medical Genetics, Department of Genetics, University of Leicester, Leicester, UK
    Am J Respir Crit Care Med 173:793-7. 2006
    ....
  61. ncbi Association between body weight of newborn rats and density of serotonin transporters in the frontal cortex at adulthood
    S Himpel
    Department of Psychiatry and Psychotherapy, University of Göttingen and University Hospital, Erlangen, Germany
    J Neural Transm 113:295-302. 2006
    ..It is discussed that differences in birth weight may affect the postnatal development of 5-HT projections to the frontal cortex...
  62. ncbi Is the platelet serotonin transporter different in venous vs. arterial blood?
    Emiliano Villa
    Molecular Physiology and Bioimaging Institute, CNR, Sezione di Genova, Via De Toni 5, 16132, Genova, Italy
    Neurochem Res 30:1365-7. 2005
    The binding of labelled paroxetine to the serotonin transporter (SERT) of platelet membranes has been studied in both venous and mixed venous/arterial blood of the rat...
  63. ncbi The distribution of serotonin transporter immunoreactivity in hippocampal formation in monkeys and rats
    Toshimi Owashi
    Department of Psychiatry, Showa University School of Medicine, 1 5 8, Hatanodai, Shinagawa, Tokyo 142 8666, Japan
    Brain Res 1010:166-8. 2004
    To elucidate the anatomical distribution of the serotonergic neurotransmitter system, we identified serotonin transporter (5-HTT) in the hippocampus of rats and monkeys by immunohistochemistry...
  64. ncbi Characterization of the serotonin transporter knockout rat: a selective change in the functioning of the serotonergic system
    J R Homberg
    Hubrecht Laboratory, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Neuroscience 146:1662-76. 2007
    ..Here, we describe the functional characterization of the serotonin transporter (SERT) knockout rat model, that is generated by N-ethyl-N-nitrosurea (ENU)-driven target-selected ..
  65. ncbi Alternative non-coding exons support serotonin transporter mRNA expression in the brain and gut
    N Ozsarac
    Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA
    J Neurochem 82:336-44. 2002
    A number of studies in recent years have linked polymorphisms within the serotonin transporter (5HTT) gene to affective disorders and anxiety traits...
  66. pmc Glycosyl modification facilitates homo- and hetero-oligomerization of the serotonin transporter. A specific role for sialic acid residues
    Deniz Ozaslan
    Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA
    J Biol Chem 278:43991-4000. 2003
    The serotonin transporter (SERT) is an oligomeric glycoprotein with two sialic acid residues on each of two complex oligosaccharide molecules...
  67. ncbi Acceleration of serotonin transporter transport-associated current by 3,4-methylenedioxymethamphetamine (MDMA) under acidic conditions
    Yosuke Yamauchi
    Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo ku, Kyoto 606 8501, Japan
    Neurosci Lett 428:72-6. 2007
    ..MDMA) selectively releases serotonin (5-HT) from neurons after uptake by the serotonin transporter (SERT) and causes psychostimulant effects accompanied by hyperthermia...
  68. ncbi Serotonin transporter deficiency in rats improves inhibitory control but not behavioural flexibility
    Judith R Homberg
    Hubrecht Institute, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Eur J Neurosci 26:2066-73. 2007
    ..In the present study we addressed the effect of lifelong reduced or absent serotonin transporter (SERT) function, which is associated with constitutively increased extracellular 5-HT levels, on ..
  69. ncbi High-dose fenfluramine administration decreases serotonin transporter binding, but not serotonin transporter protein levels, in rat forebrain
    Richard B Rothman
    Clinical Psychopharmacology Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA
    Synapse 50:233-9. 2003
    ..of D-fenfluramine (D-FEN) or parachloroamphetamine (PCA) can produce long-lasting decreases in serotonin transporter (SERT) binding and tissue levels of serotonin (5-HT) in rat forebrain...
  70. ncbi Association of the serotonin transporter gene with serum cholesterol levels and heart disease
    D E Comings
    Department of Medical Genetics, City of Hope National Medical Center, Duarte, California, 91910, USA
    Mol Genet Metab 67:248-53. 1999
    ..serum cholesterol levels and the HTTLPR insertion/deletion polymorphism of the promoter region of the serotonin transporter gene (HTT, SLC6A4)...
  71. pmc Oligomerization of serotonin transporter and its functional consequences
    F Kilic
    Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, P O Box 208066, New Haven, CT 06520 8066, USA
    Proc Natl Acad Sci U S A 97:3106-11. 2000
    Two forms of serotonin transporter (SERT) were prepared with different epitope tags. When co-expressed in HeLa cells, the form containing a FLAG tag (Res-FLAG) was associated with the form containing a c-myc tag (Sens-myc)...
  72. ncbi Cloning of a serotonin transporter affected by antidepressants
    B J Hoffman
    Laboratory of Cell Biology, National Institute of Mental Health, Bethesda, MD 20892
    Science 254:579-80. 1991
    ..The 5HT transporter has significant homology to the gamma-aminobutyric acid, dopamine, and norepinephrine transporters...
  73. ncbi Cloning and expression of a functional serotonin transporter from rat brain
    R D Blakely
    Department of Anatomy and Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322
    Nature 354:66-70. 1991
    ..3-kilobase brainstem complementary DNA clone is sufficient to confer expression of a Na(+)-dependent 5HT transporter upon nonneural cells, with transport selectively and potently antagonized by 5HT uptake-specific ..
  74. ncbi The pulmonary hypertensive fawn-hooded rat has a normal serotonin transporter coding sequence
    A M Gonzalez
    Respiratory Medicine, Division of Clinical Science, University of Sheffield Medical School, Sheffield, United Kingdom
    Am J Respir Cell Mol Biol 19:245-9. 1998
    The coding sequence of the serotonin transporter gene was compared in two strains of rat-the Wistar and the fawn-hooded rat (FHR). The FHR has an inherited platelet storage-pool deficiency and a widespread impairment of serotonin storage...
  75. pmc Estradiol increases Pet-1 and serotonin transporter mRNA in the midbrain raphe nuclei of ovariectomized rats
    Heidi M Rivera
    Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, FL 32306 4301, USA
    Brain Res 1259:51-8. 2009
    ..Further studies are required to determine whether the increased expression of Pet-1 and 5-HTT mRNA plays a causal role in the anorexigenic effect of estradiol...
  76. doi Body distribution of infused serotonin in rats
    A Elizabeth Linder
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan 48824, USA
    Clin Exp Pharmacol Physiol 36:599-601. 2009
    ....
  77. doi 1-(Aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes and 6-(aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes: a new series of potent and selective triple reuptake inhibitors
    Fabrizio Micheli
    Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline Medicine Research Centre, Via Fleming 4, 37135 Verona, Italy
    J Med Chem 53:2534-51. 2010
    ..Among these compounds, microdialysis and in vivo experiments confirm that derivative 15 has an appropriate developability profile to be considered for further progression...
  78. doi Conserved role for the serotonin transporter gene in rat and mouse neurobehavioral endophenotypes
    A V Kalueff
    Department of Pharmacology, Tulane University Medical School, New Orleans, LA 70112, USA
    Neurosci Biobehav Rev 34:373-86. 2010
    The serotonin transporter knockout (SERT(-/-)) mouse, generated in 1998, was followed by the SERT(-/-) rat, developed in 2006...
  79. doi Involvement of serotonin transporter extracellular loop 1 in serotonin binding and transport
    Yuxin Mao
    Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA
    Mol Membr Biol 25:115-27. 2008
    Residues Tyr-110 through Gly-115 of serotonin transporter were replaced, one at a time, with cysteine...
  80. ncbi Pentylenetetrazol-kindling of seizures selectively decreases [3H]-citalopram binding in the CA-3 area of rat hippocampus
    J Szyndler
    Department of Experimental and Clinical Pharmacology, Medical University, 26 28 Krakowskie Przedmiescie Street, 00 927 Warsaw, Poland
    Neurosci Lett 335:49-53. 2002
    ..This effect was accompanied by a loss of neurons and activation of microglia in the hippocampal formation. The present data suggest the important role for CA3- serotonergic innervation in pentylenetetrazol induced kindling of seizures...
  81. doi Serotonin transporter dosage modulates long-term decision-making in rat and human
    Judith R Homberg
    Department of Cognitive Neuroscience, Donders Centre for Neuroscience, UMC St Radboud, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands
    Neuropharmacology 55:80-4. 2008
    ..role in everyday life and is often disturbed in psychiatric conditions affected by the common human serotonin transporter promoter length polymorphism (5-HTTLPR)...

Research Grants8

  1. Dopamine D4 Receptor in Sustained Attention
    Kehong Zhang; Fiscal Year: 2003
    ..The findings may also provide a pharmacological basis for innovative treatment for ADHD to replace stimulant therapy. ..
  2. Gene-Gene Interactions in Pulmonary Hypertension
    ELISABETH WILLERS; Fiscal Year: 2006
    ....
  3. Arterial 5-HT Transporter Function
    Stephanie Watts; Fiscal Year: 2007
    ..Our overall hypothesis is that the serotonin transporter (SERT) is present in peripheral arteries and has physiological consequence in arterial function...
  4. Arterial 5-HT Transporter Function
    Stephanie Watts; Fiscal Year: 2009
    ..Our overall hypothesis is that the serotonin transporter (SERT) is present in peripheral arteries and has physiological consequence in arterial function...
  5. Computational and Biochemical Docking of Dopamine Transporter Antagonists
    Roxanne A Vaughan; Fiscal Year: 2010
    ....