Effects of Methylphenidate and Atomoxetine on Development of the Brain

  • Berrin Zuhal Altunkaynak
  • Mehmet Emin Onger
  • Aysin Pınar Turkmen
  • Kıymet Kubra Yurt
  • Gamze Altun
  • Murat Yuce
  • Suleyman Kaplan


The development of the neuronal system is a long and highly complex process. Similarly, brain development, while it is part of this process, entails more complex molecular mechanisms and hormonal changes that are independent of this process. Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disease that is generally seen in children and adolescents. Psychostimulants such as methylphenidate (MPH) have been commonly used for the treatment of ADHD. However, atomoxetine (ATX), a non-stimulant noradrenalin (NA) reuptake blocker, is used as an alternative for the therapy of ADHD. Exposure to these drugs gives rise to behavioral, functional, and physiological effects on the brain during the postnatal developmental period. This chapter provides general information about the brain development process and the effects of MPH and ATX on neurodevelopment in the light of the actual findings and the literature.


Attention Deficit Hyperactivity Disorder Dentate Gyrus Brain Development Bulimia Nervosa Attention Deficit Hyperactivity Disorder 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Abikoff H, Hechtman L, Klein RG, Weiss G, Fleiss K, Etcovitch J, Cousins L, Greenfield B, Martin D, Pollack S. Symptomatic improvement in children with ADHD treated with long-term methylphenidate and multimodal psychosocial treatment. J Am Acad Child Adolesc Psychiatry. 2004;43:802–11.CrossRefPubMedGoogle Scholar
  2. 2.
    Abrous DN, Koehl M, LeMoal M. Adult neurogenesis: from precursors to network and physiology. Physiol Rev. 2005;85:523–69.CrossRefPubMedGoogle Scholar
  3. 3.
    Ahdab-Barmada M, Moossy J, Nemoto EM, Lin MR. Hyperoxia produces neuronal necrosis in the rat. J Neuropathol Exp Neurol. 1986;45:233–46.CrossRefPubMedGoogle Scholar
  4. 4.
    Amano T, Ujihara H, Matsubayashi H, Sasa M, Yokota T, Tamura Y, Akaike A. Dopamine-induced protection of striatal neurons against kainate receptor-mediatedglutamate cytotoxicity in vitro. Brain Res. 1994;655:61–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Ambrogini P, Cuppini R, Ferri P, Mancini C, Ciaroni S, Voci A, Gerdoni E, Gallo G. Thyroid hormones affect neurogenesis in the dentate gyrus of adult rat. Neuroendocrinology. 2005;81:244–53.CrossRefPubMedGoogle Scholar
  6. 6.
    Andersen SL. Stimulants and the developing brain. Trends Pharmacol Sci. 2005;26:237–43.CrossRefPubMedGoogle Scholar
  7. 7.
    Andersen SL, Navalta CP. Altering the course of neurodevelopment: a framework for understanding the enduring effects of psychotropic drugs. Int J Dev Neurosci. 2004;22:423–40.CrossRefPubMedGoogle Scholar
  8. 8.
    Arnsten AF, Li BM. Neurobiology of executive functions: catecholamine influences on prefrontal cortical functions. Biol Psychiatry. 2005;57:1377–84.CrossRefPubMedGoogle Scholar
  9. 9.
    Arnsten AF, Steere JC, Hunt RD. The contribution of alpha-2 noradrenergic mechanisms of prefrontal corti- cal cognitive function: potential significance for atten- tion deficit hyperactivity disorder. Arch Gen Psychiatry. 1996;53:448–55.CrossRefPubMedGoogle Scholar
  10. 10.
    Baird AL, Coogan AN, Kaufling J, Barrot M, Thome J. Daily methylphenidate and atomoxetine treatment impacts on clock gene protein expression in the mouse brain. Brain Res. 2013;1513:61–71.CrossRefPubMedGoogle Scholar
  11. 11.
    Banerjee PS, Aston J, Khundakar AA, Zetterstrom TS. Differential regulation of psychostimulant-induced gene expression of brain derived neurotrophic factor and the immediate-early gene Arc in the juvenile and adult brain. Eur J Neurosci. 2009;29:465–76.CrossRefPubMedGoogle Scholar
  12. 12.
    Bari A, Aston-Jones G. Atomoxetine modulates spontaneous and sensory-evoked discharge of locus coeruleus noradrenergic neurons. Neuropharmacology. 2013;64:53–64.CrossRefPubMedGoogle Scholar
  13. 13.
    Barkley RA. Attention deficit hyperactivity disorder: a handbook of diagnosis and treatment, vol. 38. New York: The Guilford Press; 1996. p. 573–612.Google Scholar
  14. 14.
    Barkovich AJ. Magnetic resonance techniques in the assessment of myelin and myelination. J Inherit Metab Dis. 2005;28:311–43.CrossRefPubMedGoogle Scholar
  15. 15.
    Bartl J, Link P, Schlosser C, Gerlach M, Schmitt A, Walitza S, Riederer P, Grunblatt E. Effects of methylphenidate: the cellular point of view. Atten Defic Hyperact Disord. 2010;2:225–32.CrossRefPubMedGoogle Scholar
  16. 16.
    Bartl J, Mori T, Riederer P, Ozawa H, Grünblatt E. Methylphenidate enhances neural stem cell differentiation. J Mol Psychiatry. 2013;1:5.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Barzilai A, Daily D, Zilkha-Falb R, Ziv I, Offen D, Melamed E, Shirvan A. The molecular mechanisms of dopamine toxicity. Adv Neurol. 2003;91:73–82.PubMedGoogle Scholar
  18. 18.
    Benes FM, Turtle M, Khan Y, Farol P. Myelination of a key relay zone in the hippocampal formation occurs in the human brain during childhood, adolescence, and adulthood. Arch Gen Psychiatry. 1994;51:477–84.CrossRefPubMedGoogle Scholar
  19. 19.
    Berman SB, Hastings TG. Dopamine oxidation alters mitochondrial respiration and induces permeability transition in brain mitochondria: implications for Parkinson’s disease. J Neurochem. 1999;73:1127–37.CrossRefPubMedGoogle Scholar
  20. 20.
    Bethancourt JA, Camarena ZZ, Britton GB. Exposure to oral methylphenidate from adolescence through young adulthood produces transient effects on hippocampal-sensitive memory in rats. Behav Brain Res. 2009;202:50–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Biederman J, Spencer T, Wilens T. Evidence-based pharmaco- therapy for attention-deficit hyperactivity disorder. Int J Neuropsychopharmacol. 2004;7:77–97.CrossRefPubMedGoogle Scholar
  22. 22.
    Biederman J, Spencer T. Attention-deficit/hyperactivity disorder (ADHD) as a noradrenergic disorder. Biol Psychiatry. 1999;46:1234–42.CrossRefPubMedGoogle Scholar
  23. 23.
    Bolanos CA, Barrot M, Berton O, Wallace-Black D, Nestler EJ. Methylphenidate treatment during pre and periadolescence alters behavioral responses to emotional stimuli at adulthood. Biol Psychiatry. 2003;54:1317–29.CrossRefPubMedGoogle Scholar
  24. 24.
    Bolden-Watson C, Richelson E. Blockade by newly developed antidepressants of biogenic amine uptake into rat brain synaptosomes. Life Sci. 1993;52:1023–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Bozzi Y, Borrelli E. Dopamine in neurotoxicity and neuroprotection: what do D2 receptors have to do with it? Trends Neurosci. 2006;29:67–74.CrossRefGoogle Scholar
  26. 26.
    Brake WG, Zhang TY, Diorio J, Meaney MJ, Gratton A. Influence of early postnatal rearing conditions on mesocorticolimbic dopamine and behavioural responses to psychostimulants and stressors in adult rats. Eur J Neurosci. 2004;19:1863–74.CrossRefPubMedGoogle Scholar
  27. 27.
    Brandon CL, Marinelli M, Baker LK, White FJ. Enhanced reactivity and vulnerability to cocaine following methylphenidate treatment in adolescent rats. Neuropsychopharmacology. 2001;25:651–61.CrossRefPubMedGoogle Scholar
  28. 28.
    Brandon CL, Marinelli M, White FJ. Adolescent exposure to methylphenidate alters the activity of rat midbrain dopamine neurons. Biol Psychiatry. 2003;54:1338–44.CrossRefPubMedGoogle Scholar
  29. 29.
    Brenhouse HC, Andersen SL. Developmental trajectories during adolescence in males and females: a cross-species understanding of underlying brain changes. Neurosci Biobehav. 2011;35:1687–703.CrossRefGoogle Scholar
  30. 30.
    Brown RW, Hughes BA, Hughes AB, Sheppard AB, Perna MK, Ragsdale WL. Sex and dose-related differences in methylphenidate adolescent locomotor sensitization and effects on brain-derived neurotrophic factor. J Psychopharmacol. 2012;26:1480–8.CrossRefPubMedGoogle Scholar
  31. 31.
    Bymaster FP, Katner JS, Nelson DL, Hemrick-Luecke SK, Threlkeld PG, Heiligenstein JH, Morin SM, Gehlert DR, Perry KW. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology. 2002;27:699–711.CrossRefPubMedGoogle Scholar
  32. 32.
    Cabezas R, El-Bacha RS, Gonzalez J, Barreto GE. Mitochondrial functions in astrocytes: neuroprotective implications from oxidative damage by rotenone. Neurosci Res. 2012;74:80–90.CrossRefPubMedGoogle Scholar
  33. 33.
    Cadet JL, Brannock C. Free radicals and the pathobiology of brain dopamine systems. Neurochem Int. 1998;32:117–31.CrossRefPubMedGoogle Scholar
  34. 34.
    Cameron HA, McKay RD. Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus. J Comp Neurol. 2001;435:406–17.CrossRefPubMedGoogle Scholar
  35. 35.
    Cameron HA, Woolley CS, McEwen BS, Gould E. Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat. Neuroscience. 1993;56:337–44.CrossRefPubMedGoogle Scholar
  36. 36.
    Carmona S, Vilarroya O, Bielsa A, Tremols V, Soliva JC, Rovira M, Tomas J, Raheb C, Gispert JD, Batlle S, Bulbena A. Global and regional gray matter reductions in ADHD: a voxel-based morphometric study. Neurosci Lett. 2005;389:88–93.CrossRefPubMedGoogle Scholar
  37. 37.
    Carlezon Jr WA, Mague SD, Andersen SL. Enduring behavioral effects of early exposure to methylphenidate in rats. Biol Psychiatry. 2003;54:1330–7.CrossRefPubMedGoogle Scholar
  38. 38.
    Castellanos FX, Giedd JN, Marsh WL, Hamburger SD, Vaituzis AC, Dickstein DP, Sarfatti SE, Vauss YC, Snell JW, Lange N, Kaysen D, Krain AL, Ritchie GF, Raja- pakse JC, Rapoport JL. Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder. Arch Gen Psychiatry. 1996;53:607–16.CrossRefPubMedGoogle Scholar
  39. 39.
    Castellanos FX, Sharp PP, Jeffries W, Greenstein NO, Clasen DK, Blumenthal LS, James JD, Ebens RS, Walter CL, Zijdenbos JM, Evans A, Giedd AC, Rapoport JN. Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. JAMA. 2002;288:1740–8.CrossRefPubMedGoogle Scholar
  40. 40.
    Cayre M, Canoll P, Goldman JE. Cell migration in the normal and pathological postnatal mammalian brain. Prog Neurobiol. 2009;88:41–63.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Cepeda C, Colwell CS, Itri JN, Gruen E, Levine MS. Dopaminergic modulation of early signs of excitotoxicity in visualized rat neostriatal neurons. Eur J Neurosci. 1998;10:3491–7.CrossRefPubMedGoogle Scholar
  42. 42.
    Cooper JR, Bloom FE, Roth RH. Dopamine. The biochemical basis of neuropharmacology. New York: Oxford University Press; 1996. p. 293–351.Google Scholar
  43. 43.
    Courchesne E, Chisum HJ, Townsend J, Cowles A, Covington J, Egaas B, Harwood M, Hinds S, Press GA. Normal brain development and aging: quantitative analysis at in vivo MR imaging in healthy volunteers. Radiology. 2000;216:672–82.CrossRefPubMedGoogle Scholar
  44. 44.
    Daily D, Barzilai A, Offen D, Kamsler A, Melamed E, Ziv I. The involvement of p53 in dopamine-induced apoptosis of cerebellar granule neurons and leukemic cells over- expressing p53. Cell Mol Neurobiol. 1999;19:261–76.CrossRefPubMedGoogle Scholar
  45. 45.
    Daily D, Vlamis-Gardikas A, Offen D, Mittelman L, Melamed E, Holmgren A, Barzilai A. Glutaredoxin protects cerebellar granule neurons from dopamine-induced apoptosis by activating NF-kB via Ref-1. J Biol Chem. 2001;276:1335–44.CrossRefPubMedGoogle Scholar
  46. 46.
    Davydov BI, Drobyshev VI, Ushakov IB, Fyodorov VP. Morphological analysis of animal brain reactions to short-term hyperoxia. Kosm Biol Aviakosm Med. 1988;22:56–62.PubMedGoogle Scholar
  47. 47.
    Dawirs RR, Hildebrandt K, Teuchert-Noodt G. Adult treatment with haloperidol increases dentate granule cell proliferation in the gerbil hippocampus. J Neural Transm. 1998;105:317–27.CrossRefPubMedGoogle Scholar
  48. 48.
    Delgado PL, Miller HL, Salomon RM, Licinio J, Heninger GR, Gelenberg AJ, Charney DS. Monoamines and the mechanism of antidepressant action: effects of catecholamine depletion on mood of patients treated with antidepressants. Psychopharmacol Bull. 1993;29:389–96.PubMedGoogle Scholar
  49. 49.
    Diane CL, Jessica KY, Carlos AB, Amelia JE. Juvenile administration of methylphenidate attenuates adult hippocampal neurogenesis. Biol Psychiatry. 2006;60:1121–30.CrossRefGoogle Scholar
  50. 50.
    Ding YS, Naganawa M, Gallezot JD, Nabulsi N, Lin SF, Ropchan J, et al. Clinical doses of atomoxetine significantly occupy both norepinephrine and serotonin transports: implications on treatment of depression and ADHD. Neuroimage. 2014;86:164–71.CrossRefPubMedGoogle Scholar
  51. 51.
    Dommett EJ, Henderson EL, Westwell MS, Greenfield SA. Methylphenidate amplifies long-term plasticity in the hippocampus via noradrenergic mechanisms. Learn Mem. 2008;15:580–6.CrossRefPubMedGoogle Scholar
  52. 52.
    Donkelaar HJT, Lammens M, Hori A. Clinical neuroembryology-development and developmental disorders of the human central nervous system. Germany: Springer Science; 2006. p. 201–40.Google Scholar
  53. 53.
    Durston S, Hulshoff Pol HE, Schnack HG, Buitelaar JK, Steenhuis MP, Minderaa RB, Kahn RS, van Engeland H. Magnetic resonance imaging of boys with attention-deficit/hyperactivity disorder and their unaffected siblings. J Am Acad Child Adolesc Psychiatry. 2004;43:131–40.CrossRefGoogle Scholar
  54. 54.
    Eisch AJ, Harburg GC. Opiates, psychostimulants, and adult hippocampal neurogenesis: insights for addiction and stem cell biology. Hippocampus. 2006;16:271–86.CrossRefPubMedGoogle Scholar
  55. 55.
    Ercan ES, Çuhadaroğlu Çeti̇n F, Mukaddes MN, Yazgan Y. Di̇kkat eksi̇kli̇ği̇ hi̇perakti̇vi̇te bozukluğu tedavi̇si̇nde atomokseti̇n. Çocuk Gençlik Ruh Sağlığı Dergisi. 2009;16:113–8.Google Scholar
  56. 56.
    Fagundes AO, Rezin GT, Zanette F, Grandi E, Assis LC, Dal-Pizzol F, Quevedo J, Streck EL. Chronic administration of methylphenidate activates mitochondrial respiratory chain in brain of young rats. Int J Dev Neurosci. 2007;25:47–51.CrossRefPubMedGoogle Scholar
  57. 57.
    Faraone SV, Biederman J. Attention-deficit hyperactivity disorder. Lancet. 2005;366:237–48.CrossRefPubMedGoogle Scholar
  58. 58.
    Federici M, Geracitano R, Bernardi G, Mercuri NB. Actions of methyl- phenidate on dopaminergic neurons of the ventral midbrain. Biol Psychiatry. 2005;57:361–5.CrossRefPubMedGoogle Scholar
  59. 59.
    Ferchmin PA, Eterovic VA. Forty minutes of experience increase the weight and RNA content of cerebral cortex in periadolescent rats. Dev Psychobiol. 1986;19:511–9.CrossRefPubMedGoogle Scholar
  60. 60.
    Frantz GD, McConnell SK. Restriction of late cerebral cortical progenitors to an upper-layer fate. Neuron. 1996;17:55–61.CrossRefPubMedGoogle Scholar
  61. 61.
    Gehlert DR, Schober DA, Hemrick-Luecke SK, Krushinski J, Howbert JJ, Robertson DW, Fuller RW, Wong DT. Novel halogenated analogs of tomoxetine that are potent and selective inhibitors of norepinephrine uptake in brain. Neurochem Int. 1995;26:47–52.CrossRefPubMedGoogle Scholar
  62. 62.
    Giedd JN, Blumenthal J, Jeffries NO, Castellanos FX, Liu H, Zijdenbos A, Paus T, Evans AC, Rapoport JL. Brain development during childhood and adolescence: a longitudinal MRI study. Nat Neurosci. 1999;2:861–3.CrossRefPubMedGoogle Scholar
  63. 63.
    Giedd JN, Castellanos FX, Casey BJ, Kozuch P, King AC, Hamburger SD, Rapoport JL. Quantitative morphology of the corpus callosum. Attention deficit, hyperactivity disorder. Am J Psychiatry. 1994;151:665–9.CrossRefPubMedGoogle Scholar
  64. 64.
    Gomes KM, Inacio CG, Valvassori SS, Reus GZ, Boeck CR, Dal-Pizzol F, Quevedo J. Superoxide production after acute and chronic treatment with methylphenidate in young and adult rats. Neurosci Lett. 2009;465:95–8.CrossRefPubMedGoogle Scholar
  65. 65.
    Gould E, Beylin A, Tanapat P, Reeves A, Shors TJ. Learning enhances adult neurogenesis in the hippocampal formation. Nat Neurosci. 1999;2:260–5.CrossRefPubMedGoogle Scholar
  66. 66.
    Graham DG, Tiffany SM, Bell Jr WR, Gutknecht WF. Autoxidation versus covalent binding of quinones as the mechanism of toxicity of dopamine, 6-hydroxydopa- mine, and related compounds toward C1300 neuroblastoma cells in vitro. Mol Pharmacol. 1978;14:644–53.PubMedGoogle Scholar
  67. 67.
    Grund T, Lehmann K, Bock N, Rothenberger A, Teuchert-Noodt G. Influence of methylphenidate on brain development – an update of recent animal experiments. Behav Brain Funct. 2006;10:2.CrossRefGoogle Scholar
  68. 68.
    Guerdjikova AI, McElroy SL. Adjunctive methylphenidate in the treatment of bulimia nervosa co-occurring with bipolar disorder and substance dependence. Innov Clin Neurosci. 2013;10:30–3.PubMedPubMedCentralGoogle Scholar
  69. 69.
    Halliwell B. Oxidative stress and neurodegeneration: where are we now? J Neurochem. 2006;97:1634–58.CrossRefPubMedGoogle Scholar
  70. 70.
    Han DD, Gu HH. Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs. BMC Pharmacol. 2006;6:6.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Hastings NB, Gould E. Neurons inhibit neurogenesis. Nat Med. 2003;9:264–6.CrossRefPubMedGoogle Scholar
  72. 72.
    Hermens DF, Rowe DL, Gordon E, Williams LM. Integrative neuroscience approach to predict ADHD stimulant response. Expert Rev Neurother. 2006;6:753–63.CrossRefPubMedGoogle Scholar
  73. 73.
    Heron C, Costentin J, Bonnet JJ. Evidence that pure uptake inhibitors including cocaine interact slowly with the dopa- mine neuronal carrier. Eur J Pharmacol. 1994;264:391–8.CrossRefPubMedGoogle Scholar
  74. 74.
    Heyser CJ, Pelletier M, Ferris JS. The effects of methylphenidate on novel object exploration in weanling and periadolescent rats. Ann N Y Acad Sci. 2004;1021:465–9.CrossRefPubMedGoogle Scholar
  75. 75.
    Hill DE, Yeo RA, Campbell RA, Hart B, Vigil J, Brooks W. Magnetic rosonance imaging correlates of attention-deficit/hyperactivity disorder in children. Neuropsychology. 2003;17:496–506.CrossRefPubMedGoogle Scholar
  76. 76.
    Hou ST, et al. Increased expression of the transcription factor E2F1 during dopamine-evoked, caspase-3-mediated apoptosis in rat cortical neurons. Neurosci Lett. 2001;306:153–6.CrossRefPubMedGoogle Scholar
  77. 77.
    Hüppi PS, Warfield S, Kikinis R, Barnes PD, Zientara GP, Jolesz FA, Tsuji MK, Volpe JJ. Quantitative magnetic resonance imaging of brain development in premature and mature newborns. Ann Neurol. 1998;43:224–35.CrossRefPubMedGoogle Scholar
  78. 78.
    Iwasaki N, Hamano K, Okada Y, Horigome Y, Nakayama J, Takeya T, Takita H, Nose T. Volumetric quantification of brain development using MRI. Neuroradiology. 1997;39:841–6.CrossRefPubMedGoogle Scholar
  79. 79.
    Jakel RJ, Maragos WF. Neuronal cell death in Huntington’s disease: a potential role for dopamine. Trends Neurosci. 2000;23:239–45.CrossRefPubMedGoogle Scholar
  80. 80.
    Jensen PS, Hinshaw SP, Kraemer HC, Lenora N, Newcorn JH, Abikoff HB, March JS, Arnold LE, Cantwell DP, Conners CK, Elliott GR, Greenhill LL, Hechtman L, Hoza B, Pelham WE, Severe JB, Swanson JM, Wells KC, Wigal T, Vitiello B. ADHD Comorbidity findings from the MTA Study: comparing comorbid subgroups. J Am Acad Child Adolesc Psychiatry. 2001;40:147–58.Google Scholar
  81. 81.
    Jernigan TL, Trauner DA, Hesselink JR, Tallal PA. Maturation of human cerebrum observed in vivo during adolescence. Brain. 1991;114:2037–49.CrossRefPubMedGoogle Scholar
  82. 82.
    Keller A, Bagorda F, Hildebrandt K, Teuchert-Noodt G. Effects of enriched and of restricted rearing on both neurogenesis and synaptogenesis in the hippocampal dentate gyrus of adult gerbils (merionesunguiculatus). Neurol Psychiatr Br. 2000;8:101–8.Google Scholar
  83. 83.
    Kemner JE, Starr HL, Ciccone PE, Wood CGH, Crockett RS. Outcomes of OROS® methylphenidate compared with atomoxetine in children with ADHD: a multicenter, randomized prospective study. Adv Ther. 2005;22:498–512.CrossRefPubMedGoogle Scholar
  84. 84.
    Kennedy DN, Makris N, Herbert MR, Takahashi T, Caviness Jr VS. Basic principles of MRI and morphometry studies of human brain development. Dev Sci. 2002;5:268–78.CrossRefGoogle Scholar
  85. 85.
    Kim H, Heo HI, Kim DH, Ko IG, Lee SS, Kim SE, Kim BK, Kim TW, Ji ES, Kim JD, Shin MS, Choi YW, Kim CJ. Treadmill exercise and methylphenidate ameliorate symptoms of attention deficit/hyperactivity disorder through enhancing dopamine synthesis and brain-derived neurotrophic factor expression in spontaneous hypertensive rats. Neurosci Lett. 2010;504:35–9.CrossRefGoogle Scholar
  86. 86.
    Kinney HC, Brody BA, Kloman AS, Gilles FHJ. Sequence of central nervous system myelination in human infancy. II. Patterns of myelination in autopsied infants. Neuropathol Exp Neurol. 1988;47:217–34.CrossRefGoogle Scholar
  87. 87.
    Kitamura Y, Kakimura J, Taniguchi T. Antiparkinsonian drugs and their neuroprotective effects. Biol Pharm Bull. 2002;25:284–90.CrossRefPubMedGoogle Scholar
  88. 88.
    Kratochvil CJ, Wilens TE, Greenhill LL, Gao H, Baker KD, Feldman PD. Effects of long-term atomoxetine treatment for young children with attention-deficit/hyperactivity disorder. J Am Acad Child Psychiatry. 2006;45:919–27.CrossRefGoogle Scholar
  89. 89.
    Kuan CY, Roth KA, Flavell RA, Rakic P. Mechanisms of programmed cell death in the developing brain. Trends Neurosci. 2000;23:291–7.CrossRefPubMedGoogle Scholar
  90. 90.
    Kuczenski R, Segal DS. Exposure of adolescent rats to oral methylphenidate: preferential effects on extracellular norepinephrine and absence of sensitization and cross-sensitization to methamphetamine. J Neurosci. 2002;22:7264–71.PubMedGoogle Scholar
  91. 91.
    Kuczenski R, Segal DS. Stimulant actions in rodents: implications for attention-deficit/hyperactivity disorder treatment and potential substance abuse. Biol Psychiatry. 2005;57:1391–6.CrossRefPubMedGoogle Scholar
  92. 92.
    Kuhn HG, Biebl M, Wilhelm D, Li M, Friedlander RM, Winkler J. Increased generation of granule cells in adult Bcl-2-overexpressing mice: a role for cell death during continued hippocampal neurogenesis. Eur J Neurosci. 2005;22:1907–15.CrossRefPubMedGoogle Scholar
  93. 93.
    Lauder JM. Neurotransmitters as morphogens. Prog Brain Res. 1988;73:365–87.CrossRefPubMedGoogle Scholar
  94. 94.
    LeBlanc-Duchin D, Taukulis HK. Chronic oral methylphenidate administration to periadolescent rats yields prolonged impairment of memory for objects. Neurobiol Learn Mem. 2007;88:312–20.CrossRefPubMedGoogle Scholar
  95. 95.
    Lee HT, Lee CH, Kim IH, Yan BC, Park JH, Kwon S, Park OK, Ahn JH, Cho JH, Won M, Kim SK. Effects of ADHD therapeutic agents, methylphenidate and atomoxetine, on hippocampal neurogenesis in the adolescent mouse dentate gyrus. Neurosci Lett. 2012;524:84–8.CrossRefPubMedGoogle Scholar
  96. 96.
    Lloyd SA, Balest ZR, Corotto FS, Smeyne RJ. Cocaine selectively increases proliferation in the adult murine hippocampus. Neurosci Lett. 2010;485:112–6.CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Ludolph AG, Udvardi PT, Schaz U, Henes C, Adolph O, Weigt HU, et al. Atomoxetine acts as an NMDA receptor blocker in clinically relevant concentrations. Br J Pharmacol. 2010;160:283–91.CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Markowitz JS, DeVane CL, Pestreich LK, Patrick KS, Muniz R. A comprehensive in vitro screening of d-, l-, and dl-threo-methylphenidate: an exploratory study. J Child Adolesc Psychopharmacol. 2006;16:687–98.CrossRefPubMedGoogle Scholar
  99. 99.
    Martins MR, Reinke A, Petronilho FC, Gomes KM, Dal-Pizzol F, Quevedo J. Methylphenidate treatment induces oxidative stress in young rat brain. Brain Res. 2006;1078:189–97.CrossRefPubMedGoogle Scholar
  100. 100.
    Mattson MP. Neurotransmitters in the regulation of neuronal cytoarchitecture. Brain Res. 1988;472:179–212.CrossRefPubMedGoogle Scholar
  101. 101.
    McConnell SK, Kaznowski CE. Cell cycle dependence of laminar determination in developing neocortex. Science. 1991;254:282–5.CrossRefPubMedGoogle Scholar
  102. 102.
    McTigue DM, Tripathi RB. The life, death, and replacement of oligodendrocytes in the adult CNS. J Neurochem. 2008;107:1–19.CrossRefPubMedGoogle Scholar
  103. 103.
    Mehta MA, Owen AM, Sahakian BJ, Mavaddat N, Pickard JD, Robbins TW. Methylphenidate enhances working memory by modulating discrete frontal and parietal lobe regions in the human brain. J Neurosci. 2000;20:6.Google Scholar
  104. 104.
    Michel PP, Hefti F. Toxicity of 6-hydroxydopamine and dopamine for dopaminergic neurons in culture. J Neurosci Res. 1990;26:428–35.CrossRefPubMedGoogle Scholar
  105. 105.
    Moll GH, Hause S, Ruther E, Rothenberger A, Huether G. Early methylphenidate administration to young rats causes a persistent reduction in the density of striatal dopamine transporters. J Child Adolesc Psychopharmacol. 2001;11:15–24.CrossRefPubMedGoogle Scholar
  106. 106.
    Michelson D, Adler L, Spencer T, Reimherr FW, West SA, Allen AJ, Kelsey D, Wernicke J, Dietrich A, Milton D. Atomoxetine in adults with adhd: two randomized, placebo-controlled studies. Biol Psychiatry. 2003;53:112–20.CrossRefPubMedGoogle Scholar
  107. 107.
    Michelson D, Faries D, Wernicke J, Kelsey D, Kendrick K, Sallee FR, Spencer T. Atomoxetine in the treat- ment of children and adolescents with Attention-Defi- cit/Hyperactivity Disorder: a randomized, placebo-con- trolled, dose–response study. Pediatrics. 2001;108:e83.CrossRefPubMedGoogle Scholar
  108. 108.
    Michelson D. Active comparator studies in the atomoxetine clinical development program. Presented at: 51st Annual Meeting of the American Academy of Child and Adolescent Psychiatry. 2004; San Francisco. p. 19–24.Google Scholar
  109. 109.
    Moore KL, Persaud TVN. Before we are born: essentials of embryology and birth defects. Philadelphia: Saunders; 2002. p. 37–61.Google Scholar
  110. 110.
    Moore KL, Persaud TVN. The developing human clinically oriented embryology. Philadelphia: Elsevier Science; 2003. p. 427–62.Google Scholar
  111. 111.
    Morange M. The misunderstood gene. Cambridge, MA: Harvard University Press; 2001.Google Scholar
  112. 112.
    Mostofsky SH, Cooper KL, Kates WR, Denckla MB, Kaufmann WE. Smaller prefrontal and premotor volumes in boys with attention-deficit/hiyperactivity disorder. Biol Psychiatry. 2002;52:785–94.CrossRefPubMedGoogle Scholar
  113. 113.
    Newcorn JH, Kratochvil CJ, Allen AJ, Casat CD, Ruff DD, Moore RJ, Michelson D. Atomoxetine and osmotically released methylphenidate for the treatment of attention deficit hyperactivity disorder: acute comparison and differential response. Am J Psychiatry. 2008;165:721–30.CrossRefPubMedGoogle Scholar
  114. 114.
    O’Neill MJ, et al. Dopamine D2 receptor agonists protect against ischaemia-induced hippocampal neurodegeneration in global cerebral ischaemia. Eur J Pharmacol. 1998;352:37–46.CrossRefPubMedGoogle Scholar
  115. 115.
    Offen D, Hochman A, Gorodin S, Ziv I, Shirvan A, Barzilai A, Melamed E. Oxidative stress and neuroprotection in Parkinson’s disease: implications from studies on dopamine-induced apoptosis. Adv Neurol. 1999;80:265–9.PubMedGoogle Scholar
  116. 116.
    Page G, Peeters M, Najimi M, Maloteaux JM, Hermans E. Modulation of the neuronal dopamine transporter activity by the metabotropic glutamate receptor mGluR5 in rat striatal synaptosomes through phosphorylation mediated processes. J Neurochem. 2001;76:1282–90.CrossRefPubMedGoogle Scholar
  117. 117.
    Pakkenberg B, Gundersen HJ. Neocortical neuronnumber in humans: effect of sex and age. J Comp Neurol. 1997;384:312–20.CrossRefPubMedGoogle Scholar
  118. 118.
    Papa M, Sergeant JA, Sadile AG. Differential expression of transcription factors in the accumbens of an animal model of ADHD. Neuroreport. 1997;8:1607–12.CrossRefPubMedGoogle Scholar
  119. 119.
    Patrick KS, Caldwell RW, Ferris RM, Breese GR. Pharmacology of the enantiomers of threo-methylphenidate. J Pharmacol Exp Ther. 1987;241:152–8.PubMedGoogle Scholar
  120. 120.
    Peterson BS, Anderson AW, Ehrenkranz R, Staib LH, Tageldin M, Colson E, Gore JC, Duncan CC, Makuch R, Ment LR. Regional brain volumes and their later neurodevelopmental correlates in term and preterm infants. Pediatrics. 2003;111:939–48.CrossRefPubMedGoogle Scholar
  121. 121.
    Pfefferbaum A, Mathalon DH, et al. A quantitative magnetic resonance imaging study of changes in brain morphol- ogy from infancy to late adulthood. Arch Neurol. 1994;51:874–87.CrossRefPubMedGoogle Scholar
  122. 122.
    Pliszka SR, McCracken JT, Maas JW. Catecholamines in attention-deficit hyperactivity disorder: current per- spectives. J Am Acad Child Adolesc Psychiatry. 1996;35:264–72.CrossRefPubMedGoogle Scholar
  123. 123.
    Porat S, Simantov R. Bcl-2 and p53: role in dopamine- induced apoptosis and differentiation. Ann N Y Acad Sci. 1999;893:372–5.CrossRefPubMedGoogle Scholar
  124. 124.
    Quinn PO. In: Nadeau KG, editor. Neurobiology of attention deficit disorder, a comprehensive guide to attention deficit disorder in adults: research, diagnosis and treatment. New York: Brunner/Mazel; 1995. p. 18–35.Google Scholar
  125. 125.
    Re ́us GZ, Scaini G, Furlanetto CB, Morais MO, Jeremias IC, Mello-Santos LM, Freitas KV, Quevedo J, Streck EL. Methylphenidate treatment leads to abnormalities on krebs cycle enzymes in the brain of young and adult rats. Neurotox Res. 2013;24:251–7.CrossRefGoogle Scholar
  126. 126.
    Sadler TW. Langman’s medical embryology. 11th ed. Philadelphia/New York: Lippincott Williams and Wilkins; 2005. p. 423–70.Google Scholar
  127. 127.
    Sairanen M, Lucas G, Ernfors P, Castren M, Castren E. Brain-derived neurotrophic factor and antidepressant drugs have different but coordinated effects on neuronal turnover, proliferation, and survival in the adult dentate gyrus. J Neurosci. 2005;25:1089–94.CrossRefPubMedGoogle Scholar
  128. 128.
    Sanno H, Shen X, Kuru N, Bormuth I, Bobsin K, Gardner HAR, Komljenovic D, Tarabykin V, Erzurumlu RS, Tucker KL. Control of postnatal apoptosis in the neocortex by RhoA-Subfamily GTPases determines neuronal density. J Neurosci. 2010;30:4221–31.CrossRefPubMedPubMedCentralGoogle Scholar
  129. 129.
    Sauer J, Ring B, Witcher J. Clinical pharmacokinetics of atomoxetine. Clin Pharmacokinet. 2005;44:571–90.CrossRefPubMedGoogle Scholar
  130. 130.
    Scaini G, Fagundes AO, Rezin GT, Gomes KM, Zugno AI, Quevedo J, Streck EL. Methylphenidate increases creatine kinase activity in the brain of young and adult rats. Life Sci. 2008;83:795–800.CrossRefPubMedGoogle Scholar
  131. 131.
    Schaefers AT, Teuchert-Noodt G, Bagorda F, Brummelte S. Effect of postnatal methamphetamine trauma and adolescent methylphenidate treatment on adult hippocampal neurogenesis in gerbils. Eur J Pharmacol. 2009;616:86–90.CrossRefPubMedGoogle Scholar
  132. 132.
    Scherer EB, da Cunha MJ, Matte C, Schmitz F, Netto CA, Wyse AT. Methylphenidate affects memory, brain-derived neurotrophic factor immunocontent and brain acetylcholinesterase activity in the rat. Neurobiol Learn Mem. 2010;94:247–53.CrossRefPubMedGoogle Scholar
  133. 133.
    Schmitz F, Scherer EB, Machado FR, da Cunha AA, Tagliari B, Netto CA, Wyse AT. Methylphenidate induces lipid and protein damage in prefrontal cortex, but not in cerebellum, striatum and hippocampus of juvenile rats. Metab Brain Dis. 2012;27:605–12.CrossRefPubMedGoogle Scholar
  134. 134.
    Schwartz S, Correll CU. Efficacy and safety of atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder: results from a comprehensive meta-analysis and metaregression. J Am Acad Child Psychiatry. 2014;53:174–86.CrossRefGoogle Scholar
  135. 135.
    Schweri MM, Skolnick P, Rafferty MF, Rice KC, Janowsky AJ, Paul SM. [3H] Threo-(+/−)-methylphenidate binding to 3,4-dihydroxyphenylethylamine uptake sites in corpus striatum: correlation with the stimulant properties of ritalinic acid esters. J Neurochem. 1985;45:1062–70.CrossRefPubMedGoogle Scholar
  136. 136.
    Seeman P, Madras BK. Anti-hyperactivity medication: methylphenidate and amphetamine. Mol Psychiatry. 1998;3:386–96.CrossRefPubMedGoogle Scholar
  137. 137.
    Segal DS, Kuczenski R. Escalating dose-binge treatment with methyl- phenidate: role of serotonin in the emergent behavioral profile. J Pharmacol Exp Ther. 1999;291:19–30.PubMedGoogle Scholar
  138. 138.
    Semrud-Clikeman M, Pliszka SR, Lancaster J, Liotti M. Volumetric MRI differences in treatment-na ̈ıve vs chronically treated children with ADHD. Neurology. 2006;67:1023–7.CrossRefPubMedGoogle Scholar
  139. 139.
    Seress L, Abraham H, Tornoczky T, Kosztolanyi G. Cell formation in the human hippocampal formation from mid-gestation to the late postnatal period. Neuroscience. 2001;105:831–43.CrossRefPubMedGoogle Scholar
  140. 140.
    Shaw P, Kabani NJ, Lerch JP, Eckstrand K, Lenroot R, Gogtay N, Greenstein D, Clasen L, Evans A, Rapoport JL, Giedd JN, Wise SP. Neurodevelopmental trajectories of the human cerebral cortex. J Neurosci. 2008;28:3586–94.CrossRefPubMedGoogle Scholar
  141. 141.
    Singer HS. Tourette’s syndrome: from behaviour to biology. Lancet Neurol. 2005;4:149–59.CrossRefPubMedGoogle Scholar
  142. 142.
    Singh N, Singh DK, Aga P, Singh R. Multiple neural tube defects in a child: a rare developmental anomaly. Surg Neurol Int. 2012;3:147.CrossRefPubMedPubMedCentralGoogle Scholar
  143. 143.
    Sobel LJ, Bansal R, Maia TV, Sanchez J, Mazzone L, Durkin K. Basal ganglia surface morphology and the effects of stimulant medications in youth with attention deficit hyper- activity disorder. J Am Psychiatry. 2010;167:977–86.CrossRefGoogle Scholar
  144. 144.
    Solanto MV, Arnsten AFT, Castellanos FX. Stimulant drugs and ADHD: basic and clinical neuroscience. New York: Oxford University Press; 1998. p. 259–82.Google Scholar
  145. 145.
    Sowell ER, Thompson PM, Leonard CM, Welcome SE, Kan E, Toga AW. Longitudinal mapping of cortical thickness and brain growth in normal children. J Neurosci. 2004;24:8223–31.CrossRefPubMedGoogle Scholar
  146. 146.
    Sowell ER, Trauner DA, Gamst A, Jernigan TL. Development of cortical and subcortical brain structures in childhood and adolescence: a structural MRI study. Dev Med Child Neurol. 2002;44:4–16.CrossRefPubMedGoogle Scholar
  147. 147.
    Spemann H, Mangold H. Induction of embryonic primordia by implantation of organizers from a different species. Int J Dev Biol. 2001;45:13–38.PubMedGoogle Scholar
  148. 148.
    Spencer JT, Kratochvil JC, Sangal RB. Effects of atomoxetine on growth in children with attention deficit/hyperactivity disorder following up to five years of treatment. J Am Acad Child Psychiatry. 2006;17:689–99.Google Scholar
  149. 149.
    Spencer T, Biederman J, Wilens T, et al. Effectiveness and tolerability of tomoxetine in adults with attention deficit hyperactivity disorder. J Am Psychiatry. 1998;155:693–5.CrossRefGoogle Scholar
  150. 150.
    Spencer TJ, Newcorn JH, Kratochvil CJ, et al. Effects of atomoxetine on growth after 2-year treatment among pediatric patients with attention-deficit/hyperactivity disorder. Pediatrics. 2005;116:e74–80.CrossRefPubMedGoogle Scholar
  151. 151.
    Stahl SM. Essential psychopharmocology neuro-scientific basis and practical applications. New York: Cambridge University Press; 2000.Google Scholar
  152. 152.
    Starr HL, Kemner J. Multicenter, randomized, open-label study of OROS methylphenidate versus atomoxetine: treatment outcomes in African-American children with ADHD. J Natl Med Assoc. 2005;97 Suppl 10:11S–6.PubMedPubMedCentralGoogle Scholar
  153. 153.
    Stiles J. The fundamentals of brain development: integrating nature and nurture. Cambridge, MA: Harvard University Press; 2008.Google Scholar
  154. 154.
    Swanson CJ, Perry KW, Koch-Krueger S, Katner J, Svensson KA, Bymaster FP. Effect of the attention deficit/hyperactivity disorder drug atomoxetine on extracellular concentrations of norepinephrine and dopamine in several brain regions of the rat. Neuropharmacology. 2006;50:755–60.CrossRefPubMedGoogle Scholar
  155. 155.
    Sulzer D, Bogulavsky J, Larsen KE, Behr G, Karatekin E, Kleinman MH, Turro N, Krantz D, Edwards RH, Greene LA, Zecca L. Neuromelaninbiosynthesis is driven by excess cytosolic catecholamines not accumulated by synaptic vesicles. Proc Natl Acad Sci. 2000;97:11869–74.CrossRefPubMedPubMedCentralGoogle Scholar
  156. 156.
    Swanson JM, Volkow ND. Pharmacokinetic and pharmacodynamic properties of stimulants: implications for the design of new treatments for ADHD. Behav Brain Res. 2002;130:73–8.CrossRefPubMedGoogle Scholar
  157. 157.
    Tatsumi M, Groshan K, Blakely RD, Richelson E. Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997;340:249–58.CrossRefPubMedGoogle Scholar
  158. 158.
    Teicher MH, Andersen SL, Hostetter JC. Evidence for dopamine receptor pruning between adolescence and adulthood in striatum but not nucleus accumbens. Brain Res Dev Brain Res. 1995;89:167–72.CrossRefPubMedGoogle Scholar
  159. 159.
    Togo W, Thompson PM, Sowell ER. Mapping brain maturation. Trends Neurosci. 2006;29:148–59.CrossRefGoogle Scholar
  160. 160.
    de Haes JI U, Maguire RP, Jager PL, Paans AMJ, den Boer JA. Methylphenidate-induced activation of the anterior cingulate but not the striatum: a 15O H2O PET study in healthy volunteers. Hum Brain Mapp. 2007;28:625–35.CrossRefGoogle Scholar
  161. 161.
    Urban KR, Li Y, Gao W. Treatment with a clinically- relevant dose of methylphenidate alters NMDA receptor composition and synaptic plasticity in the juvenile rat prefrontal cortex. Neurobiol Learn Mem. 2013;101:65–74.CrossRefPubMedPubMedCentralGoogle Scholar
  162. 162.
    Urban KR, Waterhouse BD, Gao WJ. Distinct age-dependent effects of methylphenidate on developing and adult prefrontal neurons. Biol Psychiatry. 2012;72:880–8.CrossRefPubMedPubMedCentralGoogle Scholar
  163. 163.
    Vaidya CJ. Neurodevelopmental abnormalities in ADHD. Curr Top Behav Neurosci. 2012;9:49–66.CrossRefPubMedPubMedCentralGoogle Scholar
  164. 164.
    Van der Marel K, Klomp A, Meerhoff GF, Schipper P, Lucassen PJ, Homberg JR, Dijkhuizen RM, Reneman L. Long-term oral methylphenidate treatment in adolescent and adult rats: differential effects on brain morphology and function. Neuropsychopharmacology. 2014;39:263–73.CrossRefPubMedGoogle Scholar
  165. 165.
    Vanderschuren LJ, Kalivas PW. Alterations in dopaminergic and glutamatergic transmission in the induction and expression of behavioral sensitization: a critical review of preclinical studies. Psychopharmacology (Berl). 2000;151:99–120.CrossRefGoogle Scholar
  166. 166.
    Vekrellis K, McCarthy MJ, Watson A, Whitfield J, Rubin LL, Ham J. Bax promotes neuronal cell death and is downregulated during the development of the nervous system. Development. 1997;124:1239–49.PubMedGoogle Scholar
  167. 167.
    Vingilis E, Mann RE, Erickson P, Toplak M, Kolla NJ, Seeley J, Jain U. Attention deficit dyperactivity disorder, other mental health problems, substance use, and driving: examination of a population-based, representative Canadian sample. Traffic Inj Prev. 2014;15:1–9.Google Scholar
  168. 168.
    Virmani A, Gaetani F, Imam S, Binienda Z, Ali S. The protective role of L-carnitine against neurotoxicity evoked by drug of abuse, methamphetamine, could be related to mitochondrial dysfunction. Ann N Y Acad Sci. 2002;965:225–32.CrossRefPubMedGoogle Scholar
  169. 169.
    Voeller K. Attention deficit hyperactivity disorder. J Child Neurol. 2004;19:798–814.Google Scholar
  170. 170.
    Volkow ND, Fowler JS, Wang G, Ding Y, Gatley SJ. Mechanism of action of methylphenidate: insights from PET imaging studies. J Atten Disord. 2002;6:31–43.Google Scholar
  171. 171.
    Volkow ND, Wang GJ, Fowler JS, Logan J, Angrist B, Hitzemann R, Lieberman J, Pappas N. Effects of methylphenidate on regional brain glucose metabolism in humans: relationship to dopamine D-2 receptors. Am J Psychiatry. 1997;154:50–5.CrossRefPubMedGoogle Scholar
  172. 172.
    Wagner GC, Ricaurte GA, Johanson CE, Schuster CR, Seiden LS. Amphetamine induces depletion of dopamine and loss of dopamine uptake sites in caudate. Neurology. 1980;30:547–50.CrossRefPubMedGoogle Scholar
  173. 173.
    Wayment HK, Deutsch H, Schweri MM, Schenk JO. Effects of methylphenidate analogues on phenethylamine substrates for the striatal dopamine transporter: potential as amphetamine antagonists? J Neurochem. 1999;72:1266–74.CrossRefPubMedGoogle Scholar
  174. 174.
    Wietecha LA, Williams DW, Herbert M, Melmed RD, Greenbaum M, Schuh K. Atomoxetine treatment in adolescents with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2009;19:719–30.Google Scholar
  175. 175.
    Wigal S, McGough J, McCracken JT. Among classroom study of amphetamine XR and atom- oxetine for ADHD. Presented at the 51st Annual Meeting of the American Acedemy of Child Adolescent Psychiatry, Washington, DC, 2004.Google Scholar
  176. 176.
    Wilens TE, Dodson W. A clinical perspective of attention-deficit/hyperactivity disorder into adulthood. J Clin Psychiatry. 2004;65:1301–13.CrossRefPubMedGoogle Scholar
  177. 177.
    Wilens TE. Effects of methylphenidate on the catecholaminergic system in attention deficit/hyperactivity disorder. J Clin Psychopharmacol. 2008;S46–53.Google Scholar
  178. 178.
    Wong DT, Threlkeld PG, Best KL, Bymaster FP. A new inhibitor of norepinephrine uptake devoid of affinity for receptors in rat brain. J Pharmacol Exp Ther. 1982;222:61–5.PubMedGoogle Scholar
  179. 179.
    Yuan J, McCann U, Ricaurte G. Methylphenidate and brain dopamine neurotoxicity. Brain Res. 1997;767:172–5.CrossRefPubMedGoogle Scholar
  180. 180.
    Zametkin AJ, Rapoport JL. Noradrenergic hypothesis of attention deficit disorder with hyperactivity: a critical review. In: Meltzer HY, editor. Psychopharmacol the third generation of progress. New York: Raven; 1987. p. 837–47.Google Scholar
  181. 181.
    Ziv I, Melamed E, Nardi N, Luria D, Achiron A, Offen D, Barzilai A. Dopamine induces apoptosis-like cell death in cultured chick sympathetic neurons -a possible novel pathogenetic mechanism in Parkinson’s disease. Neurosci Lett. 1994;170:136–40.CrossRefPubMedGoogle Scholar

Copyright information

© Springer India 2016

Authors and Affiliations

  • Berrin Zuhal Altunkaynak
    • 1
  • Mehmet Emin Onger
    • 1
  • Aysin Pınar Turkmen
    • 1
  • Kıymet Kubra Yurt
    • 1
  • Gamze Altun
    • 1
  • Murat Yuce
    • 2
    • 1
  • Suleyman Kaplan
    • 1
  1. 1.Department of Histology and Embryology, Medical School, Medical FacultyOndokuz Mayıs UniversitySamsunTurkey
  2. 2.Department of Child and Adolescent Psychiatry, Medical SchoolOndokuz Mayıs UniversitySamsunTurkey

Personalised recommendations