J Addict Dis 13:191–199 Celik L, Sinning S, Severinsen K, Hansen CG, Moller MS, Bols M, Wiborg O, Schiott B 2008 Binding of serotonin to the human serotonin transporter.. Annu Rev Pharma
Trang 17 Parkinson’s Disease (PD)
Parkinson’s disease (PD) is characterized by rigidity in movement, resting tremor, bradykinesia, and difficulty in maintaining postural stability (Gelb et al., 1999 ) PD
is a neurodegenerative disease marked by Lewy bodies or abnormal protein aggre-gates and the loss of dopaminergic cells in the substantia nigra (Gelb et al., 1999 ) These dopaminergic neurons project into the striatum Disruption of these neural circuits inhibits pathways responsible for controlling movement The cause of PD is generally unknown However, the progressive loss of dopaminergic neurons has led researchers to examine the role of the dopamine system in PD.
Postmortem studies show a correlation between PD and DAT concentrations in the striatum (Niznik et al., 1991 ) Molecular imaging techniques have been used
to determine DAT levels using DAT radiotracers such as 2 β-carbomethoxy-3β-(4-iodophenyl) tropane ([123I] β-CIT) and [11C] cocaine (Shih et al., 2006 ) These techniques are useful for the evaluation and diagnosis of patients with PD and to monitor the progression of the disease (Shih et al., 2006 ) The delivery of DA
to surviving nerve terminals by treatment with L-DOPA helps alleviate some of the early symptoms of PD (Nutt, 2002 ) Unfortunately, the ameliorating effects of
L-DOPA fade and within five years of treatment approximately half of patients display involuntary, sometimes debilitating dyskinesias (Bezard et al., 2001 ) This reduced ability ofL-DOPA to treat patients is thought to result from a failing ability
to store synthesized DA (Lee et al., 2008 ) The reduction in the ability to store DA
is thought to result from the immediate release of all DA synthesized fromL-DOPA (Lee et al., 2008 ) Lee and colleagues demonstrated that the sprouting of DA termi-nals and decreased DAT function help to prevent the appearance of PD symptoms until approximately 60% of dopaminergic neurons in the substantia nigra are lost (Lee et al., 2008 ) They proposed that the DA terminal sprouting and decreased DAT function helped contribute to the DA release responsible for the reduced therapeutic benefits ofL-DOPA (Lee et al., 2008 ).
8 Important Findings and the Need for Future Studies
Significant advances have been made in understanding the role of the monoamine transporters in the pathology of disease states Despite these advances, studies are needed to further elucidate monoamine transporter structure and function In recent years, genetic animal models exhibiting disruption of the monoamine transporters have provided a unique method for investigating the role of these transporters in physiology and pathology Studies with DAT, SERT, and NET knock-out mice are able to reveal subtle interplay among these transporters (Gainetdinov and Caron, 2003 ) Knock-out of individual transporters exposes secondary functions and compensatory mechanisms of the remaining monoamine transporters.
The development of improved pharmacological agents targeting the monoamine transporters has been hindered by a lack of structural information Although numer-ous biochemical and molecular studies have provided insight into the structural and
Trang 2mechanistic aspects of monoamine transporter function, to date no crystal struc-ture exists Yamashita and colleagues provided a significant contribution to the field with the crystallization of LeuTAa(Yamashita et al., 2005 ) and further information was revealed with the subsequent cocrystallization of LeuTAawith the TCAs (Singh
et al., 2007 ; Zhou et al., 2007 ) These structures have allowed for homology mod-eling of the monoamine transporters and have revitalized the structural studies of these transporters (Indarte et al., 2008 ; Jorgensen et al., 2007a , b; Celik et al., 2008 ; Forrest et al., 2007 ; White et al., 2006 ).
Important discoveries have been made in the findings of transporter gene poly-morphisms The identification of promoter polymorphisms and coding region polymorphisms in individuals has helped to link these variations with disease states Further studies are needed to understand the genetic and environmental contribu-tions of these variants to disease Additionally, a number of regulatory mechanisms and interacting proteins have been identified for the monoamine transporters Future studies will need to identify additional players in this complex network of interac-tions A greater understanding of this network will be vital in understanding and treating diseases such as addiction, ADHD, autism, and PD.
Acknowledgments Special thanks to David Allen for all of his help with figure construction.
References
Apparsundaram S, Galli A, DeFelice LJ, Hartzell HC, Blakely RD (1998a) Acute regula-tion of norepinephrine transport: I Protein kinase C-linked muscarinic receptors influence transport capacity and transporter density in SK-N-SH cells J Pharmacol Exp Ther 287: 733–743
Apparsundaram S, Schroeter S, Giovanetti E, Blakely RD (1998b) Acute regulation of nore-pinephrine transport: II PKC-modulated surface expression of human norenore-pinephrine trans-porter proteins J Pharmacol Exp Ther 287:744–751
Arndt IO, Dorozynsky L, Woody GE, McLellan AT, O’Brien CP (1992) Desipramine treatment of cocaine dependence in methadone-maintained patients Arch Gen Psychiatry 49:888–893 Balkovetz DF, Tiruppathi C, Leibach FH, Mahesh VB, Ganapathy V (1989) Evidence for an imipramine-sensitive serotonin transporter in human placental brush-border membranes J Biol Chem 264:2195–2198
Barnes NM, Sharp T (1999) A review of central 5-HT receptors and their function Neuropharmacology 38:1083–1152
Barr CL, Xu C, Kroft J, Feng Y, Wigg K, Zai G, Tannock R, Schachar R, Malone M, Roberts W, Nothen MM, Grunhage F, Vandenbergh DJ, Uhl G, Sunohara G, King N, Kennedy JL (2001) Haplotype study of three polymorphisms at the dopamine transporter locus confirm linkage to attention-deficit/hyperactivity disorder Biol Psychiatry 49:333–339
Batki SL, Washburn AM, Delucchi K, Jones RT (1996) A controlled trial of fluoxetine in crack cocaine dependence Drug Alcohol Depend 41:137–142
Bauman AL, Apparsundaram S, Ramamoorthy S, Wadzinski BE, Vaughan RA, Blakely RD (2000) Cocaine and antidepressant-sensitive biogenic amine transporters exist in regulated complexes with protein phosphatase 2A J Neurosci 20:7571–7578
Benmansour S, Cecchi M, Morilak DA, Gerhardt GA, Javors MA, Gould GG, Frazer A (1999) Effects of chronic antidepressant treatments on serotonin transporter function, density, and mRNA level J Neurosci 19:10494–10501
Trang 3Benmansour S, Owens WA, Cecchi M, Morilak DA, Frazer A (2002) Serotonin clearance in vivo is altered to a greater extent by antidepressant-induced downregulation of the serotonin transporter than by acute blockade of this transporter J Neurosci 22:6766–6772
Bezard E, Brotchie JM, Gross CE (2001) Pathophysiology of levodopa-induced dyskinesia: potential for new therapies Nat Rev Neurosci 2:577–588
Borowsky B, Adham N, Jones KA, Raddatz R, Artymyshyn R, Ogozalek KL, Durkin MM, Lakhlani PP, Bonini JA, Pathirana S, Boyle N, Pu X, Kouranova E, Lichtblau H, Ochoa FY, Branchek TA, Gerald C (2001) Trace amines: identification of a family of mammalian G protein-coupled receptors Proc Natl Acad Sci USA 98:8966–8971
Boulay D, Duterte-Boucher D, Leroux-Nicollet I, Naudon L, Costentin J (1996) Locomotor sen-sitization and decrease in [3H]mazindol binding to the dopamine transporter in the nucleus accumbens are delayed after chronic treatments by GBR12783 or cocaine J Pharmacol Exp Ther 278:330–337
Buitelaar JK, Willemsen-Swinkels SH (2000) Autism: current theories regarding its pathogenesis and implications for rational pharmacotherapy Paediatr Drugs 2:67–81
Campbell JL, Thomas HM, Gabrielli W, Liskow BI, Powell BJ (1994) Impact of desipramine
or carbamazepine on patient retention in outpatient cocaine treatment: preliminary findings J Addict Dis 13:191–199
Celik L, Sinning S, Severinsen K, Hansen CG, Moller MS, Bols M, Wiborg O, Schiott B (2008) Binding of serotonin to the human serotonin transporter Molecular modeling and experimental validation J Am Chem Soc 130:3853–3865
Chen CK, Chen SL, Mill J, Huang YS, Lin SK, Curran S, Purcell S, Sham P, Asherson P (2003) The dopamine transporter gene is associated with attention deficit hyperactivity disorder in a Taiwanese sample Mol Psychiatry 8:393–396
Chen N, Justice JB (2000) Differential effect of structural modification of human dopamine transporter on the inward and outward transport of dopamine Mol Brain Res 75: 208–215
Chen NH, Reith ME, Quick MW (2004) Synaptic uptake and beyond: the sodium-and chloride-dependent neurotransmitter transporter family SLC6 Pflugers Arch 447:519–531
Churchill L, Dilts RP, Kalivas PW (1992) Autoradiographic localization of gamma-aminobutyric acidA receptors within the ventral tegmental area Neurochem Res 17:101–106
Claye LH, Akunne HC, Davis MD, DeMattos S, Soliman KF (1995) Behavioral and neurochemi-cal changes in the dopaminergic system after repeated cocaine administration Mol Neurobiol 11:55–66
Cook EH, Leventhal BL (1996) The serotonin system in autism Curr Opin Pediatr 8:348–354 Cook EH Jr., Stein MA, Krasowski MD, Cox NJ, Olkon DM, Kieffer JE, Leventhal BL (1995) Association of attention-deficit disorder and the dopamine transporter gene Am J Hum Genet 56:993–998
Curran S, Mill J, Tahir E, Kent L, Richards S, Gould A, Huckett L, Sharp J, Batten C, Fernando S, Ozbay F, Yazgan Y, Simonoff E, Thompson M, Taylor E, Asherson P (2001) Association study
of a dopamine transporter polymorphism and attention deficit hyperactivity disorder in UK and Turkish samples Mol Psychiatry 6:425–428
Daly G, Hawi Z, Fitzgerald M, Gill M (1999) Mapping susceptibility loci in attention deficit hyper-activity disorder: preferential transmission of parental alleles at DAT1, DBH and DRD5 to affected children Mol Psychiatry 4:192–196
Di Chiara G, Imperato A (1988) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats Proc Natl Acad Sci USA 85:5274–5278
Donnan GA, Kaczmarczyk SJ, Paxinos G, Chilco PJ, Kalnins RM, Woodhouse DG, Mendelsohn
FA (1991) Distribution of catecholamine uptake sites in human brain as determined by quantitative [3H] mazindol autoradiography J Comp Neurol 304:419–434
Eisenhofer G (2001) The role of neuronal and extraneuronal plasma membrane transporters in the inactivation of peripheral catecholamines Pharmacol Ther 91:35–62
Trang 4Erickson JD, Eiden LE, Hoffman BJ (1992) Expression cloning of a reserpine-sensitive vesicular monoamine transporter Proc Natl Acad Sci USA 89:10993–10997
Erickson JD, Schafer MK, Bonner TI, Eiden LE, Weihe E (1996) Distinct pharmacological prop-erties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter Proc Natl Acad Sci USA 93:5166–5171
Faham S, Watanabe A, Besserer GM, Cascio D, Specht A, Hirayama BA, Wright EM, Abramson J (2008) The crystal structure of a sodium galactose transporter reveals mechanistic insights into Na+/sugar symport Science 321:810–814
Fleckenstein AE, Volz TJ, Hanson GR (2009) Psychostimulant-induced alterations in vesicular monoamine transporter-2 function: Neurotoxic and therapeutic implications Neuropharmacology 56:133–138
Fleckenstein AE, Volz TJ, Riddle EL, Gibb JW, Hanson GR (2007) New insights into the mechanism of action of amphetamines Annu Rev Pharmacol Toxicol 47:681–698
Folstein SE, Rosen-Sheidley B (2001) Genetics of autism: complex aetiology for a heterogeneous disorder Nat Rev Genet 2:943–955
Forrest LR, Tavoulari S, Zhang YW, Rudnick G, Honig B (2007) Identification of a chloride ion binding site in Na+/Cl-dependent transporters Proc Natl Acad Sci USA 104:12761–12766 Forrest LR, Zhang YW, Jacobs MT, Gesmonde J, Xie L, Honig BH, Rudnick G (2008) Mechanism for alternating access in neurotransmitter transporters Proc Natl Acad Sci USA 105: 10338–10343
Frazer A, Benmansour S (2002) Delayed pharmacological effects of antidepressants Mol Psychiatry 7(Suppl 1):S23–S28
Gainetdinov RR, Caron MG (2003) Monoamine transporters: from genes to behavior Annu Rev Pharmacol Toxicol 43:261–284 Epub;%2002 Sep 17
Garcia AS, Barrera G, Burke TF, Ma S, Hensler JG, Morilak DA (2004) Autoreceptor-mediated inhibition of norepinephrine release in rat medial prefrontal cortex is maintained after chronic desipramine treatment J Neurochem 91:683–693
Gelb DJ, Oliver E, Gilman S (1999) Diagnostic criteria for Parkinson disease Arch Neurol 56: 33–39
Gelenberg AJ, Chesen CL (2000) How fast are antidepressants? J Clin Psychiatry 61:712–721 Gill M, Daly G, Heron S, Hawi Z, Fitzgerald M (1997) Confirmation of association between atten-tion deficit hyperactivity disorder and a dopamine transporter polymorphism Mol Psychiatry 2:311–313
Giros B, Wang YM, Suter S, McLeskey SB, Pifl C, Caron MG (1994) Delineation of dis-crete domains for substrate, cocaine, and tricyclic antidepressant interactions using chimeric dopamine-norepinephrine transporters J Biol Chem 269:15985–15988
Gonzalez G, Sevarino K, Sofuoglu M, Poling J, Oliveto A, Gonsai K, George TP, Kosten
TR (2003) Tiagabine increases cocaine-free urines in cocaine-dependent methadone-treated patients: results of a randomized pilot study Addiction 98:1625–1632
Gorelick DA (1992) Alcohol and cocaine Clinical and pharmacological interactions Recent Dev Alcohol 10:37–56
Gould GG, Pardon MC, Morilak DA, Frazer A (2003) Regulatory effects of reboxetine treatment alone, or following paroxetine treatment, on brain noradrenergic and serotonergic systems Neuropsychopharmacology 28:1633–1641
Grabowski J, Rhoades H, Elk R, Schmitz J, Davis C, Creson D, Kirby K (1995) Fluoxetine is ineffective for treatment of cocaine dependence or concurrent opiate and cocaine dependence: two placebo-controlled double-blind trials J Clin Psychopharmacol 15:163–174
Greengard P (2001) The neurobiology of dopamine signaling Biosci Rep 21:247–269
Grunhage F, Schulze TG, Muller DJ, Lanczik M, Franzek E, Albus M, Borrmann-Hassenbach
M, Knapp M, Cichon S, Maier W, Rietschel M, Propping P, Nothen MM (2000) Systematic screening for DNA sequence variation in the coding region of the human dopamine transporter gene (DAT1) Mol Psychiatry 5:275–282
Gutman DA, Owens MJ (2006) Serotonin and norepinephrine transporter binding profile of SSRIs Essent Psychopharmacol 7:35–41
Trang 5Hahn MK, Blakely RD (2007) The functional impact of SLC6 transporter genetic variation Annu Rev Pharmacol Toxicol 47:401–441
Hahn MK, Mazei-Robison MS, Blakely RD (2005) Single nucleotide polymorphisms in the human norepinephrine transporter gene affect expression, trafficking, antidepressant interaction, and protein kinase C regulation Mol Pharmacol 68:457–466
Hahn MK, Robertson D, Blakely RD (2003) A mutation in the human norepinephrine transporter gene (SLC6A2) associated with orthostatic intolerance disrupts surface expression of mutant and wild-type transporters J Neurosci 23:4470–4478
Hammoumi S, Payen A, Favre JD, Balmes JL, Benard JY, Husson M, Ferrand JP, Martin JP, Daoust M (1999) Does the short variant of the serotonin transporter linked polymorphic region constitute a marker of alcohol dependence? Alcohol 17:107–112
Han DD, Gu HH (2006) Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs BMC Pharmacol 6(6):6
Heinz A, Goldman D, Gallinat J, Schumann G, Puls I (2004) Pharmacogenetic insights to monoaminergic dysfunction in alcohol dependence Psychopharmacology (Berl) 174:561–570 Heinz A, Ragan P, Jones DW, Hommer D, Williams W, Knable MB, Gorey JG, Doty L, Geyer C, Lee KS, Coppola R, Weinberger DR, Linnoila M (1998) Reduced central serotonin transporters
in alcoholism Am J Psychiatry 155:1544–1549
Heninger GR, Delgado PL, Charney DS (1996) The revised monoamine theory of depres-sion: a modulatory role for monoamines, based on new findings from monoamine depletion experiments in humans Pharmacopsychiatry 29:2–11
Henry LK, Meiler J, Blakely RD (2007) Bound to be different: neurotransmitter transporters meet their bacterial cousins Mol Interv 7:306–309
Henry JP, Sagne C, Bedet C, Gasnier B (1998) The vesicular monoamine transporter: from chromaffin granule to brain Neurochem Int 32:227–246
Hillemacher T, Frieling H, Hartl T, Wilhelm J, Kornhuber J, Bleich S (2009) Promoter specific methylation of the dopamine transporter gene is altered in alcohol dependence and associated with craving J Psychiatr Res 43:388–392
Hjorth S, Bengtsson HJ, Kullberg A, Carlzon D, Peilot H, Auerbach SB (2000) Serotonin autoreceptor function and antidepressant drug action J Psychopharmacol 14:177–185 Hollander E, Phillips AT, Yeh CC (2003) Targeted treatments for symptom domains in child and adolescent autism Lancet 362:732–734
Howell LL, Kimmel HL (2008) Monoamine transporters and psychostimulant addiction Biochem Pharmacol 75:196–217
Indarte M, Madura JD, Surratt CK (2008) Dopamine transporter comparative molecular model-ing and bindmodel-ing site prediction usmodel-ing the LeuT(Aa) leucine transporter as a template Proteins 70:1033–1046
Jacobs BL, Azmitia EC (1992) Structure and function of the brain serotonin system Physiol Rev 72:165–229
Jayanthi LD, Ramamoorthy S (2005) Regulation of monoamine transporters: influence of psychos-timulants and therapeutic antidepressants AAPS J 7:E728–E738
Jayanthi LD, Samuvel DJ, Ramamoorthy S (2004) Regulated internalization and phosphorylation
of the native norepinephrine transporter in response to phorbol esters Evidence for localization
in lipid rafts and lipid raft-mediated internalization J Biol Chem 279:19315–19326
Jess U, Betz H, Schloss P (1996) The membrane-bound rat serotonin transporter, SERT1, is an oligomeric protein FEBS Letters 394:44–46
Johnson RG Jr (1988) Accumulation of biological amines into chromaffin granules: a model for hormone and neurotransmitter transport Physiol Rev 68:232–307
Jorgensen AM, Tagmose L, Jorgensen AM, Bogeso KP, Peters GH (2007a) Molecular dynam-ics simulations of Na+/Cl(–)-dependent neurotransmitter transporters in a membrane-aqueous system ChemMedChem 2:827–840
Jorgensen AM, Tagmose L, Jorgensen AM, Topiol S, Sabio M, Gundertofte K, Bogeso KP, Peters GH (2007b) Homology modeling of the serotonin transporter: insights into the primary escitalopram-binding site ChemMedChem 2:815–826
Trang 6Just H, Sitte HH, Schmid JA, Freissmuth M, Kudlacek O (2004) Identification of an additional interaction domain in transmembrane domains 11 and 12 that supports oligomer formation in the human serotonin transporter J Biol Chem 279:6650–6657
Keller NR, Diedrich A, Appalsamy M, Miller LC, Caron MG, McDonald MP, Shelton RC, Blakely RD, Robertson D (2006) Norepinephrine transporter-deficient mice respond to anx-iety producing and fearful environments with bradycardia and hypotension Neuroscience 139:931–946
Kilic F, Murphy DL, Rudnick G (2003) A human serotonin transporter mutation causes constitutive activation of transport activity Mol Pharmacol 64:440–446
Kilic F, Rudnick G (2000) Oligomerization of serotonin transporter and its functional conse-quences Proc Natl Acad Sci USA 97:3106–3111
Kim CH, Hahn MK, Joung Y, Anderson SL, Steele AH, Mazei-Robinson MS, Gizer I, Teicher MH, Cohen BM, Robertson D, Waldman ID, Blakely RD, Kim KS (2006) A polymorphism in the norepinephrine transporter gene alters promoter activity and is associated with attention-deficit hyperactivity disorder Proc Natl Acad Sci USA 103:19164–19169
Lee J, Zhu WM, Stanic D, Finkelstein DI, Horne MH, Henderson J, Lawrence AJ, O’Connor L, Tomas D, Drago J, Horne MK (2008) Sprouting of dopamine terminals and altered dopamine release and uptake in Parkinsonian dyskinaesia Brain 131:1574–1587
Lesch KP, Balling U, Gross J, Strauss K, Wolozin BL, Murphy DL, Riederer P (1994) Organization of the human serotonin transporter gene J Neural Transm Gen Sect 95: 157–162
Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, Benjamin J, Muller CR, Hamer
DH, Murphy DL (1996) Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region Science 274:1527–1531
Letchworth SR, Daunais JB, Hedgecock AA, Porrino LJ (1997) Effects of chronic cocaine administration on dopamine transporter mRNA and protein in the rat Brain Res 750: 214–222
Letchworth SR, Sexton T, Childers SR, Vrana KE, Vaughan RA, Davies HM, Porrino LJ (1999) Regulation of rat dopamine transporter mRNA and protein by chronic cocaine administration
J Neurochem 73:1982–1989
Levin FR, Lehman AF (1991) Meta-analysis of desipramine as an adjunct in the treatment of cocaine addiction J Clin Psychopharmacol 11:374–378
Lin Z, Madras BK (2006) Human genetics and pharmacology of neurotransmitter transporters Handb Exp Pharmacol 175:327–371
Macdonald H, Rutter M, Howlin P, Rios P, Le Conteur A, Evered C, Folstein S (1989) Recognition and expression of emotional cues by autistic and normal adults J Child Psychol Psychiatry 30:865–877
Makkonen I, Riikonen R, Kokki H, Airaksinen MM, Kuikka JT (2008) Serotonin and dopamine transporter binding in children with autism determined by SPECT Dev Med Child Neurol 50:593–597
Mash DC, Pablo J, Ouyang Q, Hearn WL, Izenwasser S (2002) Dopamine transport function is elevated in cocaine users J Neurochem 81:292–300
Mazei-Robison MS, Bowton E, Holy M, Schmudermaier M, Freissmuth M, Sitte HH, Galli
A, Blakely RD (2008) Anomalous dopamine release associated with a human dopamine transporter coding variant J Neurosci 28:7040–7046
Melikian HE, McDonald JK, Gu H, Rudnick G, Moore KR, Blakely RD (1994) Human nore-pinephrine transporter Biosynthetic studies using a site-directed polyclonal antibody J Biol Chem 269:12290–12297
Melikian HE, Ramamoorthy S, Tate CG, Blakely RD (1996) Inability to N-glycosylate the human norepinephrine transporter reduces protein stability, surface trafficking, and transport activity but not ligand recognition Mol Pharmacol 50:266–276
Mereu G, Fadda F, Gessa GL (1984) Ethanol stimulates the firing rate of nigral dopaminergic neurons in unanesthetized rats Brain Res 292:63–69
Trang 7Milner HE, B¯eliveau R, Jarvis SM (1994) The in situ size of the dopamine transporter is a tetramer
as estimated by radiation inactivation Biochimica et Biophysica Acta (BBA) Biomembranes 1190:185–187
Morilak DA, Frazer A (2004) Antidepressants and brain monoaminergic systems: a dimensional approach to understanding their behavioural effects in depression and anxiety disorders Int J Neuropsychopharmacol 7:193–218
Murphy M, Bolton PF, Pickles A, Fombonne E, Piven J, Rutter M (2000) Personality traits of the relatives of autistic probands Psychol Med 30:1411–1424
Niznik HB, Fogel EF, Fassos FF, Seeman P (1991) The dopamine transporter is absent in parkinsonian putamen and reduced in the caudate nucleus J Neurochem 56:192–198 Nutt DJ (2002) The neuropharmacology of serotonin and noradrenaline in depression Int Clin Psychopharmacol 17(Suppl 1):S1–S12
Ogilvie AD, Battersby S, Bubb VJ, Fink G, Harmar AJ, Goodwim GM, Smith CA (1996) Polymorphism in serotonin transporter gene associated with susceptibility to major depression Lancet 347:731–733
Olivier JD, Van Der Hart MG, Van Swelm RP, Dederen PJ, Homberg JR, Cremers T, Deen
PM, Cuppen E, Cools AR, Ellenbroek BA (2008) A study in male and female 5-HT trans-porter knockout rats: an animal model for anxiety and depression disorders Neuroscience 152: 573–584
Owens MJ, Morgan WN, Plott SJ, Nemeroff CB (1997) Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites J Pharmacol Exp Ther 283:1305–1322 Ozaki N, Goldman D, Kaye WH, Plotnicov K, Greenberg BD, Lappalainen J, Rudnick G, Murphy
DL (2003) Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype Mol Psychiatry 8:933–936
Padbury JF, Tseng YT, McGonnigal B, Penado K, Stephan M, Rudnick G (1997) Placental biogenic amine transporters: cloning and expression Brain Res Mol Brain Res 45:163–168
Pardo CA, Eberhart CG (2007) The neurobiology of autism Brain Pathol 17:434–447
Pilotte NS, Sharpe LG, Kuhar MJ (1994) Withdrawal of repeated intravenous infusions of cocaine persistently reduces binding to dopamine transporters in the nucleus accumbens of Lewis rats
J Pharmacol Exp Ther 269:963–969
Ramamoorthy S, Giovanetti E, Qian Y, Blakely RD (1998) Phosphorylation and regulation of antidepressant-sensitive serotonin transporters J Biol Chem 273:2458–2466
Ramamoorthy S, Samuvel DJ, Buck ER, Rudnick G, Jayanthi LD (2007) Phosphorylation of thre-onine residue 276 is required for acute regulation of serotonin transporter by cyclic GMP J Biol Chem 20(282):11639–11647
Rothman RB, Baumann MH (2003) Monoamine transporters and psychostimulant drugs Eur J Pharmacol 479:23–40
Rudnick G (2007) What is an antidepressant binding site doing in a bacterial transporter? ACS Chem Biol 2:606–609
Saldana SN, Barker EL (2004) Temperature and 3,4-methylenedioxymethamphetamine alter human serotonin transporter-mediated dopamine uptake Neurosci Lett 354:209–212 Samuvel DJ, Jayanthi LD, Bhat NR, Ramamoorthy S (2005) 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 J Neurosci 25:29–41
Schmitz Y, Schmauss C, Sulzer D (2002) Altered dopamine release and uptake kinetics in mice lacking D2 receptors J Neurosci 22:8002–8009
Schroeter S, Levey AI, Blakely RD (1997) Polarized expression of the antidepressant-sensitive serotonin transporter in epinephrine-synthesizing chromaffin cells of the rat adrenal gland Mol Cell Neurosci 9:170–184
Schuldiner S, Shirvan A, Linial M (1995) Vesicular neurotransmitter transporters: from bacteria to humans Physiol Rev 75:369–392
Seidel S, Singer EA, Just H, Farhan H, Scholze P, Kudlacek O, Holy M, Koppatz K, Krivanek
P, Freissmuth M, Sitte HH (2005) Amphetamines take two to tango: an oligomer-based
Trang 8counter-transport model of neurotransmitter transport explores the amphetamine action Mol Pharmacol 67:140–151
Shannon JR, Flattem NL, Jordan J, Jacob G, Black BK, Biaggioni I, Blakely RD, Robertson
D (2000) Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency N Engl J Med 342:541–549
Shih MC, Hoexter MQ, Andrade LA, Bressan RA (2006) Parkinson’s disease and dopamine transporter neuroimaging: a critical review Sao Paulo Med J 124:168–175
Shoptaw S, Yang X, Rotheram-Fuller EJ, Hsieh YC, Kintaudi PC, Charuvastra VC, Ling W (2003) Randomized placebo-controlled trial of baclofen for cocaine dependence: preliminary effects for individuals with chronic patterns of cocaine use J Clin Psychiatry 64:1440–1448 Singh SK, Yamashita A, Gouaux E (2007) Antidepressant binding site in a bacterial homologue of neurotransmitter transporters Nature 448:952–956
Sitte HH, Farhan H, Javitch JA (2004) Sodium-dependent neurotransmitter TRANSPORTERS: OLIGOMERIZATION as a determinant of transporter function and trafficking Mol Interv 4:38–47
Sofuoglu M, Kosten TR (2005) Novel approaches to the treatment of cocaine addiction CNS Drugs 19:13–25
Song F, Freemantle N, Sheldon TA, House A, Watson P, Long A, Mason J (1993) Selective serotonin reuptake inhibitors: meta-analysis of efficacy and acceptability BMJ 306: 683–687
Steffensen SC, Svingos AL, Pickel VM, Henriksen SJ (1998) Electrophysiological characterization
of GABAergic neurons in the ventral tegmental area J Neurosci 18:8003–8015
Sulzer D, Chen TK, Lau YY, Kristensen H, Rayport S, Ewing A (1995) Amphetamine redistributes dopamine from synaptic vesicles to the cytosol and promotes reverse transport J Neurosci 15:4102–4108
Talvenheimo J, Rudnick G (1980) Solubilization of the platelet plasma membrane serotonin transporter in an active form J Biol Chem 255:8606–8611
Tella SR, Ladenheim B, Andrews AM, Goldberg SR, Cadet JL (1996) Differential reinforcing effects of cocaine and GBR-12909: biochemical evidence for divergent neuroadaptive changes
in the mesolimbic dopaminergic system J Neurosci 16:7416–7427
Torres GE, Carneiro A, Seamans K, Fiorentini C, Sweeney A, Yao WD, Caron MG (2003b) Oligomerization and trafficking of the human dopamine transporter Mutational analysis iden-tifies critical domains important for the functional expression of the transporter J Biol Chem 278:2731–2739
Torres GE, Gainetdinov RR, Caron MG (2003a) Plasma membrane monoamine transporters: structure, regulation and function Nat Rev Neurosci 4:13–25
Vaughan RA, Huff RA, Uhl GR, Kuhar MJ (1997) Protein kinase C-mediated phosphorylation and functional regulation of dopamine transporters in striatal synaptosomes J Biol Chem 272:15541–15546
Wade PR, Chen J, Jaffe B, Kassem IS, Blakely RD, Gershon MD (1996) Localization and function of a 5-HT transporter in crypt epithelia of the gastrointestinal tract J Neurosci 16: 2352–2364
Waldman ID, Rowe DC, Abramowitz A, Kozel ST, Mohr JH, Sherman SL, Cleveland HH, Sanders
ML, Gard JM, Stever C (1998) Association and linkage of the dopamine transporter gene and attention-deficit hyperactivity disorder in children: heterogeneity owing to diagnostic subtype and severity Am J Hum Genet 63:1767–1776
Walsh SL, Preston KL, Sullivan JT, Fromme R, Bigelow GE (1994) Fluoxetine alters the effects of intravenous cocaine in humans J Clin Psychopharmacol 14:396–407
Weyand S, Shimamura T, Yajima S, Suzuki S, Mirza O, Krusong K, Carpenter EP, Rutherford NG, Hadden JM, O’Reilly J, Ma P, Saidijam M, Patching SG, Hope RJ, Norbertczak HT, Roach
PC, Iwata S, Henderson PJ, Cameron AD (2008) Structure and molecular mechanism of a nucleobase-cation-symport-1 family transporter Science 322:709–713
Trang 9White KJ, Kiser PD, Nichols DE, Barker EL (2006) Engineered zinc-binding sites confirm prox-imity and orientation of transmembrane helices I and III in the human serotonin transporter Protein Sci 15:2411–2422
White KJ, Walline CC, Barker EL (2005) Serotonin transporters: implications for antidepressant drug development AAPS J 7:E421–E433
Wilson JM, Nobrega JN, Corrigall WA, Coen KM, Shannak K, Kish SJ (1994) Amygdala dopamine levels are markedly elevated after self – but not passive-administration of cocaine Brain Res 668:39–45
Xie Z, Miller GM (2007) Trace amine-associated receptor 1 is a modulator of the dopamine transporter J Pharmacol Exp Ther 321:128–136
Xie Z, Westmoreland SV, Bahn ME, Chen GL, Yang H, Vallender EJ, Yao WD, Madras BK, Miller GM (2007) Rhesus monkey trace amine-associated receptor 1 signaling: enhancement
by monoamine transporters and attenuation by the D2 autoreceptor in vitro J Pharmacol Exp Ther 321:116–127
Xie Z, Westmoreland SV, Miller GM (2008) Modulation of monoamine transporters by com-mon biogenic amines via trace amine-associated receptor 1 and com-monoamine autoreceptors
in human embryonic kidney 293 cells and brain synaptosomes J Pharmacol Exp Ther 325: 629–640
Yamashita A, Singh SK, Kawate T, Jin Y, Gouaux E (2005) Crystal structure of a bacterial homologue of Na+/Cl-dependent neurotransmitter transporters Nature 437:215–223
Zanardi R, Benedetti F, Di Bella D, Catalano M, Smeraldi E (2000) Efficacy of paroxetine in depression is influenced by a functional polymorphism within the promoter of the serotonin transporter gene J Clin Psychopharmacol 20:105–107
Zhang YW, Gesmonde J, Ramamoorthy S, Rudnick G (2007) Serotonin transporter phosphory-lation by cGMP-dependent protein kinase is altered by a mutation associated with obsessive compulsive disorder J Neurosci 27:10878–10886
Zhou Z, Zhen J, Karpowich NK, Goetz RM, Law CJ, Reith ME, Wang DN (2007) LeuT-desipramine structure reveals how antidepressants block neurotransmitter reuptake Science 317:1390–1393
Zhu CB, Carneiro AM, Dostmann WR, Hewlett WA, Blakely RD (2005) p38 MAPK activa-tion elevates serotonin transport activity via a trafficking-independent, protein phosphatase 2A-dependent process J Biol Chem 280:15649–15658