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Effects of Methylphenidate and Atomoxetine on Development of the Brain

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Melatonin, Neuroprotective Agents and Antidepressant Therapy

Abstract

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.

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References

  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.

    Article  PubMed  Google Scholar 

  2. Abrous DN, Koehl M, LeMoal M. Adult neurogenesis: from precursors to network and physiology. Physiol Rev. 2005;85:523–69.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  6. Andersen SL. Stimulants and the developing brain. Trends Pharmacol Sci. 2005;26:237–43.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  8. Arnsten AF, Li BM. Neurobiology of executive functions: catecholamine influences on prefrontal cortical functions. Biol Psychiatry. 2005;57:1377–84.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  12. Bari A, Aston-Jones G. Atomoxetine modulates spontaneous and sensory-evoked discharge of locus coeruleus noradrenergic neurons. Neuropharmacology. 2013;64:53–64.

    Article  CAS  PubMed  Google Scholar 

  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. Barkovich AJ. Magnetic resonance techniques in the assessment of myelin and myelination. J Inherit Metab Dis. 2005;28:311–43.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  16. Bartl J, Mori T, Riederer P, Ozawa H, Grünblatt E. Methylphenidate enhances neural stem cell differentiation. J Mol Psychiatry. 2013;1:5.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  21. Biederman J, Spencer T, Wilens T. Evidence-based pharmaco- therapy for attention-deficit hyperactivity disorder. Int J Neuropsychopharmacol. 2004;7:77–97.

    Article  CAS  PubMed  Google Scholar 

  22. Biederman J, Spencer T. Attention-deficit/hyperactivity disorder (ADHD) as a noradrenergic disorder. Biol Psychiatry. 1999;46:1234–42.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  33. Cadet JL, Brannock C. Free radicals and the pathobiology of brain dopamine systems. Neurochem Int. 1998;32:117–31.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  37. Carlezon Jr WA, Mague SD, Andersen SL. Enduring behavioral effects of early exposure to methylphenidate in rats. Biol Psychiatry. 2003;54:1330–7.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  40. Cayre M, Canoll P, Goldman JE. Cell migration in the normal and pathological postnatal mammalian brain. Prog Neurobiol. 2009;88:41–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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. 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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  49. Diane CL, Jessica KY, Carlos AB, Amelia JE. Juvenile administration of methylphenidate attenuates adult hippocampal neurogenesis. Biol Psychiatry. 2006;60:1121–30.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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. 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.

    Article  Google Scholar 

  54. Eisch AJ, Harburg GC. Opiates, psychostimulants, and adult hippocampal neurogenesis: insights for addiction and stem cell biology. Hippocampus. 2006;16:271–86.

    Article  CAS  PubMed  Google Scholar 

  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. 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.

    Article  CAS  PubMed  Google Scholar 

  57. Faraone SV, Biederman J. Attention-deficit hyperactivity disorder. Lancet. 2005;366:237–48.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  60. Frantz GD, McConnell SK. Restriction of late cerebral cortical progenitors to an upper-layer fate. Neuron. 1996;17:55–61.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    PubMed  PubMed Central  Google Scholar 

  69. Halliwell B. Oxidative stress and neurodegeneration: where are we now? J Neurochem. 2006;97:1634–58.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Hastings NB, Gould E. Neurons inhibit neurogenesis. Nat Med. 2003;9:264–6.

    Article  CAS  PubMed  Google Scholar 

  72. Hermens DF, Rowe DL, Gordon E, Williams LM. Integrative neuroscience approach to predict ADHD stimulant response. Expert Rev Neurother. 2006;6:753–63.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  79. Jakel RJ, Maragos WF. Neuronal cell death in Huntington’s disease: a potential role for dopamine. Trends Neurosci. 2000;23:239–45.

    Article  CAS  PubMed  Google Scholar 

  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. Jernigan TL, Trauner DA, Hesselink JR, Tallal PA. Maturation of human cerebrum observed in vivo during adolescence. Brain. 1991;114:2037–49.

    Article  PubMed  Google Scholar 

  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. 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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  87. Kitamura Y, Kakimura J, Taniguchi T. Antiparkinsonian drugs and their neuroprotective effects. Biol Pharm Bull. 2002;25:284–90.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  89. Kuan CY, Roth KA, Flavell RA, Rakic P. Mechanisms of programmed cell death in the developing brain. Trends Neurosci. 2000;23:291–7.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  93. Lauder JM. Neurotransmitters as morphogens. Prog Brain Res. 1988;73:365–87.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  96. Lloyd SA, Balest ZR, Corotto FS, Smeyne RJ. Cocaine selectively increases proliferation in the adult murine hippocampus. Neurosci Lett. 2010;485:112–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  100. Mattson MP. Neurotransmitters in the regulation of neuronal cytoarchitecture. Brain Res. 1988;472:179–212.

    Article  CAS  PubMed  Google Scholar 

  101. McConnell SK, Kaznowski CE. Cell cycle dependence of laminar determination in developing neocortex. Science. 1991;254:282–5.

    Article  CAS  PubMed  Google Scholar 

  102. McTigue DM, Tripathi RB. The life, death, and replacement of oligodendrocytes in the adult CNS. J Neurochem. 2008;107:1–19.

    Article  CAS  PubMed  Google Scholar 

  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. Michel PP, Hefti F. Toxicity of 6-hydroxydopamine and dopamine for dopaminergic neurons in culture. J Neurosci Res. 1990;26:428–35.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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. Moore KL, Persaud TVN. Before we are born: essentials of embryology and birth defects. Philadelphia: Saunders; 2002. p. 37–61.

    Google Scholar 

  110. Moore KL, Persaud TVN. The developing human clinically oriented embryology. Philadelphia: Elsevier Science; 2003. p. 427–62.

    Google Scholar 

  111. Morange M. The misunderstood gene. Cambridge, MA: Harvard University Press; 2001.

    Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  117. Pakkenberg B, Gundersen HJ. Neocortical neuronnumber in humans: effect of sex and age. J Comp Neurol. 1997;384:312–20.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  119. Patrick KS, Caldwell RW, Ferris RM, Breese GR. Pharmacology of the enantiomers of threo-methylphenidate. J Pharmacol Exp Ther. 1987;241:152–8.

    CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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. 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.

    Article  CAS  Google Scholar 

  126. Sadler TW. Langman’s medical embryology. 11th ed. Philadelphia/New York: Lippincott Williams and Wilkins; 2005. p. 423–70.

    Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Sauer J, Ring B, Witcher J. Clinical pharmacokinetics of atomoxetine. Clin Pharmacokinet. 2005;44:571–90.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  136. Seeman P, Madras BK. Anti-hyperactivity medication: methylphenidate and amphetamine. Mol Psychiatry. 1998;3:386–96.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  141. Singer HS. Tourette’s syndrome: from behaviour to biology. Lancet Neurol. 2005;4:149–59.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  Google Scholar 

  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. 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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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. 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.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  151. Stahl SM. Essential psychopharmocology neuro-scientific basis and practical applications. New York: Cambridge University Press; 2000.

    Google Scholar 

  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.

    PubMed  PubMed Central  Google Scholar 

  153. Stiles J. The fundamentals of brain development: integrating nature and nurture. Cambridge, MA: Harvard University Press; 2008.

    Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  159. Togo W, Thompson PM, Sowell ER. Mapping brain maturation. Trends Neurosci. 2006;29:148–59.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Vaidya CJ. Neurodevelopmental abnormalities in ADHD. Curr Top Behav Neurosci. 2012;9:49–66.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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. 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.

    Article  CAS  PubMed  Google Scholar 

  169. Voeller K. Attention deficit hyperactivity disorder. J Child Neurol. 2004;19:798–814.

    Google Scholar 

  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. 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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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. 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. Wilens TE, Dodson W. A clinical perspective of attention-deficit/hyperactivity disorder into adulthood. J Clin Psychiatry. 2004;65:1301–13.

    Article  PubMed  Google Scholar 

  177. Wilens TE. Effects of methylphenidate on the catecholaminergic system in attention deficit/hyperactivity disorder. J Clin Psychopharmacol. 2008;S46–53.

    Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  179. Yuan J, McCann U, Ricaurte G. Methylphenidate and brain dopamine neurotoxicity. Brain Res. 1997;767:172–5.

    Article  CAS  PubMed  Google Scholar 

  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. 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.

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Histology and Embryology, Medical School, Medical Faculty, Ondokuz Mayıs University, Samsun, Turkey

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

  2. Department of Child and Adolescent Psychiatry, Medical School, Ondokuz Mayıs University, Samsun, Turkey

    Murat Yuce

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    Takahiro A. Kato

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Altunkaynak, B.Z. et al. (2016). Effects of Methylphenidate and Atomoxetine on Development of the Brain. In: López-Muñoz, F., Srinivasan, V., de Berardis, D., Álamo, C., Kato, T. (eds) Melatonin, Neuroprotective Agents and Antidepressant Therapy. Springer, New Delhi. https://doi.org/10.1007/978-81-322-2803-5_48

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