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Functional Consequences of Iron Overload in Catecholaminergic Interactions: the Youdim Factor

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Abstract

The influence of postnatal iron overload upon implications of the functional and interactive role of dopaminergic and noradrenergic pathways that contribute to the expressions of movement disorder and psychotic behaviours in mice was studied in a series of experiments. (1) Postnatal iron overload at doses of 7.5 mg/kg (administered on Days 10–12 post partum) and above, invariably induced a behavioural syndrome consisting of an initial (1st 20–40 min of a 60-min test session) hypoactivity followed by a later (final 20 min of a 60-min test session) hyperactivity, when the mice were tested at adult ages (age 60 days or more). (2) Following postnatal iron overload, subchronic treatment with the neuroleptic compounds, clozapine and haloperidol, dose-dependently reversed the initial hypoactivity and later hyperactivity induced by the metal. Furthermore, DA D2 receptor supersensitivity (as assessed using the apomorphine-induced behaviour test) was directly and positively correlated with iron concentrations in the basal ganglia. (3) Brain noradrenaline (NA) denervation, using the selective NA neurotoxin, DSP4, prior to administration of the selective DA neurotoxin, MPTP, exacerbated both the functional (hypokinesia) and neurochemical (DA depletion) effects of the latter neurotoxin. Treatment with L-Dopa restored motor activity only in the animals that had not undergone NA denervation. These findings suggest an essential neonatal iron overload, termed “the Youdim factor”, directing a DA–NA interactive component in co-morbid disorders of nigrostriatal-limbic brain regions.

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References

  1. Mash DC, Pablo J, Buck BE, Sanchez-Ramos J, Weiner WJ (1991) Distribution and number of transferrin receptors in Parkinson’s disease and in MPTP-treated mice. Exp Neurol 114:73–81

    PubMed  CAS  Google Scholar 

  2. Hallgren B, Sourander P (1958) The effect of age on the non-haem iron in the brain. J Neurochem 3:41–46

    PubMed  CAS  Google Scholar 

  3. Dexter DT, Carayon A, Javoy-Agid F, Agid Y, Wells FR, Daniel SE, Lees AJ, Jenner P, Marsden CD (1991) Alterations in the levels of iron, ferritin and other trace metals in Parkinson’s disease and other neurodegenerative diseases affecting the basal ganglia. Brain 114:1953–1975

    PubMed  Google Scholar 

  4. Janetzky B, Reichmann H, Youdim MBH, Riederer P (1997) Iron and oxidative damage in neurodegenerative diseases. In: Willey-Liss, Inc., pp. 407–421

  5. Youdim MBH, Ben-Shachar D, Riederer P (1991) Iron in brain function and dysfunction with emphasis on Parkinson’s disease. Eur Neurol 31:34–40

    PubMed  Google Scholar 

  6. Youdim MBH (1990) Neuropharmacological and neurochemical aspects of iron deficiency. In: Dobbing J (Ed) Brain behaviour and iron in the infant diet. Springer-Verlag, Berlin, pp 83–94

    Google Scholar 

  7. Youdim MBH, Riederer P (1997) Understanding Parkinson’s disease. Sci Am 257:59–62

    Google Scholar 

  8. Youdim MBH, Riederer P (1999) Iron in the brain, normal and pathological. In: Adelman G, Smith BH (Eds) Encyclopedia of neuroscience. Elsevier, Amsterdam, pp 983–997

    Google Scholar 

  9. Zecca L, Youdim MBH, Riederer P, Connor JR, Crichton RR (2004) Iron, brain ageing and neurodegenerative disorders. Nat Rev Neurosci 5:863–873

    PubMed  CAS  Google Scholar 

  10. Youdim MBH (2000) Nutrient deprivation and brain function: iron. Nutrition 16:504–508

    PubMed  CAS  Google Scholar 

  11. Yehuda S, Youdim MBH, Mostofsky M (1986) Brain iron deficiency causes reduced learning capacity in rats. Pharmacol Biochem Behav 24:141–146

    Google Scholar 

  12. Ben-Shachar D, Youdim MB (1990) Neuroleptic-induced supersensitivity and brain iron: I. Iron deficiency and neuroleptic-induced dopamine D2 receptor supersensitivity. J Neurochem 54:1136–1141

    PubMed  CAS  Google Scholar 

  13. Ben-Shachar D, Pinhassi B, Youdim MB (1991) Prevention of neuroleptic-induced dopamine D2 receptor supersensitivity by chronic iron salt treatment. Eur J Pharmacol 202:177–183

    PubMed  CAS  Google Scholar 

  14. Evans PH (1993) Free radicals in brain metabolism and pathology. Br Med Bull 49:577–587

    PubMed  CAS  Google Scholar 

  15. Olanow CW (1992) Magnetic-resonance-imaging in parkinsonism. Neurol Clin 10:405–420

    PubMed  CAS  Google Scholar 

  16. Strong R, Mattamal M, Andorn A (1993) Free radicals in aging. In: Free radicals, the aging brain, and age-related neurodegenerative disorders. CRC Press, Florida, pp 223–246

  17. Kienzl E, Puchinger L, Jellinger K, Linert W, Stachelberger H, Jameson RF (1995) The role of transition metals in the pathogenesis of Parkinson’s disease. J Neurol Sci 134(Suppl):69–78

    PubMed  Google Scholar 

  18. Reichmann H, Janetzky B, Riederer P (1995) Iron-dependent enzymes in Parkinson’s disease. J Neural Transm Suppl 46:157–164

    PubMed  CAS  Google Scholar 

  19. Swaiman KF (1991) Hallervorden-Spatz syndrome and brain iron metabolism. Arch Neurol 48:1285–1293

    PubMed  CAS  Google Scholar 

  20. Dexter DT, Wells FR, Agid F, Agid Y, Lees AJ, Jenner P, Marsden CD (1987) Increased nigral iron content in postmortem parkinsonian brain [letter]. Lancet 2:1219–1220

    PubMed  CAS  Google Scholar 

  21. Drayer BP, Olanow W, Burger P, Johnson GA, Herfkens R, Riederer S (1986) Parkinson plus syndrome: diagnosis using high field MR imaging of brain iron. Radiology 159:493–498

    PubMed  CAS  Google Scholar 

  22. Gerlach M, Ben-Shachar D, Riederer P, Youdim MB (1994) Altered brain metabolism of iron as a cause of neurodegenerative diseases? J Neurochem 63:793–807

    Article  PubMed  CAS  Google Scholar 

  23. Riederer P, Sofic E, Rausch WD, Schmidt B, Reynolds GP, Jellinger K, Youdim MB (1989) Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains. J Neurochem 52:515–520

    PubMed  CAS  Google Scholar 

  24. Youdim MBH, Fridkin M, Zheng H (2004) Novel bifunctional drugs targeting monoamine oxidase inhibition and iron chelation as an approach to neuroprotection in Parkinson’s disease and other neurodegenerative diseases. J Neural Transm 111:1455–1471

    PubMed  CAS  Google Scholar 

  25. Youdim MBH, Stephenson G, Ben Shachar D (2004) Ironing iron out in Parkinson’s disease and other neurodegenerative disease with iron chelators: a lesson from 6-hydroxydopamine and iron chelators, desferal and VK-28. Ann N Y Acad Sci 1012:306–325

    PubMed  CAS  Google Scholar 

  26. Zheng H, Weiner LM, Bar-Am O, Epsztejn M, Cabantchik I, Warshawsky A, Youdim MBH, Fridkin M (2005) Design, synthesis and evaluation of novel bifunctional iron-chelators as potential agents for neuroprotection in neurodegenerative diseases. Bioorg Med Chem 13:773–783

    PubMed  CAS  Google Scholar 

  27. Zheng H, Gal S, Weiner LM, Bar-Am O, Warshawsky A, Fridkin M, Youdim MBH (2005) Novel multifunctional neuroprotective iron chelator-monoamine oxidase inhibitor drugs for neurodegenerative diseases: in vitro studies on antioxidant activity, prevention of lipid peroxide formation and monoamine oxidase inhibition. J Neurochem 95:68–78

    PubMed  CAS  Google Scholar 

  28. Taylor EM, Morgan EH (1990) Developmental changes in transferrin and iron uptake by the brain in the rat. Brain Res Dev Brain Res 55:35–42

    PubMed  CAS  Google Scholar 

  29. Taylor EM, Crowe A, Morgan EH (1991) Transferrin and iron uptake by the brain: effects of altered iron status. J Neurochem 57:1584–1592

    PubMed  CAS  Google Scholar 

  30. Dwork AJ, Lawler G, Zybert PA, Durkin M, Osman M, Willson N, Barkai AI (1990) An autoradiographic study of the uptake and distribution of iron by the brain of the young rat. Brain Res 518:31–39

    PubMed  CAS  Google Scholar 

  31. Davison AN, Dobbing J (1968) Applied neurochemistry. Blackwell, Oxförd, pp 178–221, 253–316

  32. Bolles RG, Woods PJ (1964) The ontogeny of behaviour in the albino rat. Anim Behav 12:427–441

    Google Scholar 

  33. Campbell BA, Lytle LD, Fibiger HC (1969) Ontogeny of adrenergic arousal and cholinergic inhibitory mechanisms in the rat. Science 166:635–637

    PubMed  CAS  Google Scholar 

  34. Randall PK, Severson JA, Finch CE (1981) Aging and the regulation of striatal dopaminergic mechanisms in mice. J Pharmacol Exp Ther 219:695–700

    PubMed  CAS  Google Scholar 

  35. McKenzie RG, Zigmond MJ (1985) Chronic neuroleptic treatment increased D-2 but not D-1 receptors in the rat striatum. Eur J Pharmacol 113:159–165

    Google Scholar 

  36. Tarsy D, Baldessarini RJ (1974) Behavioural supersensitivity to apomorphine following treatment with drugs which interfere with synaptic function of catecholamines. Neuropharmacology 13:927–940

    PubMed  CAS  Google Scholar 

  37. Von Voigtlander PF, Losey EG, Triezenberg HF (1975) Increased sensitivity to dopaminergic agents after chronic neuroleptic treatment. J Pharmacol Exp Ther 193:88–94

    Google Scholar 

  38. Randall PK (1985) Quantification of dopaminergic supersensitivity using apomorphine induced behaviour in the mouse. Life Sci 37:1419–1423

    PubMed  CAS  Google Scholar 

  39. Scatton B (1977) Differential regional development of the tolerance to increase in dopamine turnover upon repeated neuroleptic administration. Eur J Pharmacol 46:363–369

    PubMed  CAS  Google Scholar 

  40. Laduron P, De Bie K, Leysen J (1977) Specific effect of haloperidol on dopamine turnover in the frontal cortex. Naunyn Schmiedelbergs Arch Pharmacol 296:183–185

    CAS  Google Scholar 

  41. Matsumoto T, Uchimura H, Hirano M, Soo Kim J, Yokoo H, Shimomura M, Nakahara T, Inoue K, Oomagari K (1983) Differential effects of acute and chronic administration of haloperidol on homovanillic acid levels in discrete levels of rat brain. Eur J Pharmacol 89:27–33

    PubMed  CAS  Google Scholar 

  42. Campbell A, Baldessarini RJ (1981) Tolerance to behavioural effects of haloperidol. Life Sci 29:1341–1346

    PubMed  CAS  Google Scholar 

  43. Reynolds GP, Brown JE, McCall JE, McKay AVP (1992) Dopamine receptor abnormalities in the striatum and pallidum in tardive dyskinesia: a postmortem study. J Neural Transm 87:225–230

    CAS  Google Scholar 

  44. Iqbal MM, Rahman A, Husain Z, Mahmud SZ, Ryan WG, Feldman JM (2003) Clozapine: a clinical review of adverse effects and management. Ann Clin Psychiat 15:33–48

    Google Scholar 

  45. Lieberman JA (1998) Maximizing clozapine therapy: managing side effects. J Clin Psychiat 59:38–43

    CAS  Google Scholar 

  46. Archer T, Fredriksson A (2000) Effects of clonidine and adrenoceptor antagonists on motor activity in DSP4-treated mice I: dose, time- and parameter-dependency. Neurotoxicity Res 1:235–247

    CAS  Google Scholar 

  47. Archer T, Fredriksson A (2001) Effects of α-adrenoceptor agonists in chronic morphine administered DSP4-treated rats: evidence for functional cross-sensitization. Neurotoxicity Res 3:411–432

    CAS  Google Scholar 

  48. Archer T, Ögren S-O, Johansson G, Ross SB (1982) DSP4-induced two-way active avoidance impairment: involvement of central and not peripheral noradrenaline depletion. Psychopharmacology 76:303–309

    PubMed  CAS  Google Scholar 

  49. Archer T, Mohammed AK, Ross SB, Söderberg U (1983) T-maze learning, spontaneous activity and food intake recovery following systemic administration of the noradrenaline neurotoxin, DSP4. Pharmacol Biochem Behav 19:121–130

    PubMed  CAS  Google Scholar 

  50. Archer T, Jonsson G, Ross SB (1984) A parametric study of the effects of the noradrenaline neurotoxin DSP4 on avoidance acquisition and noradrenaline neurons in the CNS of the rat. Br J Pharmacol 82:249–257

    PubMed  CAS  Google Scholar 

  51. Archer T, Fredriksson A, Jonsson G, Lewander T, Mohammed AK, Ross SB, Soderberg U (1986) Central noradrenaline depletion antagonizes aspects of d-amphetamine-induced hyperactivity in the rat. Psychopharmacology 88:141–146

    PubMed  CAS  Google Scholar 

  52. Dooley DJ, Bittiger H, Hauser KL, Bischoff SL, Waldmeier PC (1983) Alteration of central alpha 2- and beta-adrenergic receptors in the rat after DSP4, a selective noradrenergic neurotoxin. Neuroscience 9:889–898

    PubMed  CAS  Google Scholar 

  53. Frderiksson A, Archer T (2000) Effects of clonidine and α-adrenoceptor antagonists on motor activity in DSP4-treated mice II: interactions with apomorphine. Neurotoxicity Res 1:249–259

    Google Scholar 

  54. Jonsson G, Hallman H (1982) Response of central monoamine neurons following an early neurotoxic lesion. Bibl Anat 23:76–92

    PubMed  Google Scholar 

  55. Jonsson G, Hallman H, Ponzio F, Ross SB (1981) DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine)—a useful denervation tool for central and peripheral noradrenaline neurons. Europ J Pharmacol 72:173–188

    CAS  Google Scholar 

  56. Jonsson G, Hallman H, Sundström E (1982) Effects of the noradrenaline neurotoxin DSP4 on the postnatal development of central noradrenaline neurons in the rat. Neuroscience 7:2895–2907

    PubMed  CAS  Google Scholar 

  57. Ponzio F, Hallman H, Jonsson G (1981) Noradrenaline and dopamine interaction in rat brain during development. Med Biol 59:161–169

    PubMed  CAS  Google Scholar 

  58. Ross SB (1976) Long-term effects of N-2-chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride on noradrenergic neurons in the rat brain and heart. Brit J Pharmacol 58:521–527

    CAS  Google Scholar 

  59. Ross SB, Renyi L (1976) On the long-lasting inhibitory effect of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) on the active uptake of noradrenaline. J Pharmacol Pharmac 28:458–459

    CAS  Google Scholar 

  60. Archer T, Jonsson G, Ross SB (1985) Active and passive avoidance following the administration of systemic DSP4, xylamine, or p-chloroamphetamine. Behav Neural Biol 43:238–249

    PubMed  CAS  Google Scholar 

  61. Archer T (1982) Serotonin and fear retention in the rat. J Comp Physiol Psychol 96:491–516

    PubMed  CAS  Google Scholar 

  62. Archer T, Jonsson G, Minor BG, Post C (1986) Noradrenergic-serotonergic interactions and nociception in the rat. Europ J Pharmacol 120:295–307

    CAS  Google Scholar 

  63. Heal DJ, Butler SA, Prow MR, Buckett WR (1993) Quantification of alpha 2-adrenoceptors in rat brain after short-term DSP-4 lesioning. Europ J Pharmacol 249:37–41

    CAS  Google Scholar 

  64. Post C, Persson ML, Archer T, Minor BG, Danysz W, Sundström E (1987) Increased antinociception by alpha-adrenoceptor drugs after spinal cord noradrenaline depletion. Europ J Pharmacol 137:107–116

    CAS  Google Scholar 

  65. Dooley DJ, Mogilnicka E, Delini-Stula A, Waechter F, Truog A, Wood J (1983) Functional supersensitivity to adrenergic agonists in the rat after DSP-4, a selective noradrenergic neurotoxin. Psychopharmacology 81:1–5

    PubMed  CAS  Google Scholar 

  66. Fornai F, Bassi L, Torracca MT, Alessandri MG, Scalori V, Corsini GU (1996) Region- and neurotransmitter-dependent species and strain differences in DSP4-induced monoamine depletion in rodents. Neurodegeneration 5:241–249

    PubMed  CAS  Google Scholar 

  67. Langston JW (1985) MPTP neurotoxicity: an overview and characterization of phases of toxicity. Life Sci 36:201–206

    PubMed  CAS  Google Scholar 

  68. Fredriksson A, Plaznik A, Sundström E, Jonsson G, Archer T (1990) MPTP-induced hypoactivity in mice: reversal by L-Dopa. Pharmacol Toxicol 67:295–301

    Article  PubMed  CAS  Google Scholar 

  69. Sundström E, Fredriksson A, Archer T (1990) Chronic neurochemical and behavioural changes in MPTP-lesioned C57 Bl/6 mice: a model for Parkinson’s disease. Brain Res 528:181–188

    PubMed  Google Scholar 

  70. Heikkila RE, Sieber B-A, Manzino L, Sonsalla PK (1989) Some features of the nigrostriatal dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse. Mol Chem Neuropathol 10:171–183

    Article  PubMed  CAS  Google Scholar 

  71. Sonsalla PK, Heikkila RE (1986) The influence of dose and dosing interval on MPTP-induced dopaminergic neurotoxicity in mice. Europ J Pharmacol 129:339–345

    CAS  Google Scholar 

  72. Archer T, Fredriksson A (2003) An antihypokinesic action of α2-adrenoceptors upon MPTP-induced behaviour deficits in mice. J Neural Transm 110:183–200

    PubMed  CAS  Google Scholar 

  73. Fredriksson A, Archer T (1994a) MPTP-induced behavioural deficits in mice: validity and utility of a model of parkinsonism. In Palomo T, Archer T, Beningen RJ (eds) Strategies for studying brain disorders, vol 2, Schizophrenia, movement disorders and age-related disorders. University Press, Madrid, pp 201–231

  74. Fredriksson A, Archer T (1994b) MPTP-induced behavioural and biochemical deficits: a parametric analysis. J Neurol Transm 7:123–132

    CAS  Google Scholar 

  75. Fredriksson A, Palomo T, Chase TN, Archer T (1999) Tolerance to a suprathreshold dose of L-Dopa in MPTP mice: effects of glutamate antagonists. J Neural Transm 106:283–300

    PubMed  CAS  Google Scholar 

  76. Fredriksson A, Schroder N, Eriksson P, Izquierdo I, Archer T (1999) Neonatal iron exposure induces neurobehavioural dysfunctions in adult mice. Toxicol Appl Pharmacol 159:25–30

    PubMed  CAS  Google Scholar 

  77. Fredriksson A, Archer T (2003) Effect of postnatal iron administration on MPTP-induced behavioural deficits and neurotoxicity: behavioural enhancement by L-Dopa-MK-801 co-administration. Behav Brain Res 139:31–46

    PubMed  CAS  Google Scholar 

  78. Fredriksson A, Schroder N, Eriksson P, Izquierdo I, Archer T (2001) Neonatal iron potentiates adult MPTP-induced neurodegenerative and functional deficits. Parkinsonism Rel Dis 7:97–105

    Google Scholar 

  79. Persson T, Waldeck B (1970) Further studies on the possible interaction between dopamine and noradrenaline containing neurons in the brain. Europ J Pharmacol 11:315–320

    CAS  Google Scholar 

  80. Andén N-E, Grabowska M (1976) Pharmacological evidence for a stimulation of dopamine neurons by noradrenaline neurons in the brain. Europ J Pharmacol 39:275–282

    Google Scholar 

  81. Fornai F, Alessandri MG, Torracca MT, Bassi L, Corsini GU (1997) Effects of noradrenergic lesions on MPTP/MPP+ kinetics and MPTP-induced nigrostriatal dopamine depletions. J Pharmacol Exp Ther 283:100–107

    PubMed  CAS  Google Scholar 

  82. Marien MR, Briley M, Colpaert FC (1993) Noradrenaline depletion exacerbates MPTP-induced striatal dopamine loss in mice. Europ J Pharmacol 236:487–489

    CAS  Google Scholar 

  83. Nishi K, Kondo T, Narabayashi H (1991) Destruction of norepinephrine terminals in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice reduces locomotor activity induced by L-dopa. Neurosci Lett 123:244–247

    PubMed  CAS  Google Scholar 

  84. Glowinski J, Iversen LL (1966) Regional studies of catecholamines in the rat brain. I. The disposition of [3H]norepinephrine, [3H]dopamine and [3H]dopa in various regions of the brain. J Neurochem 13:655–669

    PubMed  CAS  Google Scholar 

  85. Björk L, Cornfield LJ, Nelson DL, Hillver S-E, Andén N-E, Lewander T, Hacksell U (1991) Pharmacology of the novel 5-hydroxytryptamine1A receptor antagonist (S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin: inhibition of (R)-8-hydroxy-2-(dipropylamino)tetralin-induced effects. J Pharmacol Exp Therap 258:58–65

    Google Scholar 

  86. Ye Liu Y, Yu H, Mohell N, Nordvall G, Lewander T, Hacksell U (1995) Derivatives of cis-2-amino-8-hydroxy-1-methyltetralin: mixed 5-HT1A-receptor agonists and dopamine-D2-receptor antagonists. J Med Chem 38:150–160

    Google Scholar 

  87. Kirk R (1995) Experimental design: procedures for the behavioural sciences. Brooks/Cole, Belmont, CA

    Google Scholar 

  88. Fredriksson A, Eriksson P, Archer T (2006) Postnatal Iron-induced motor behaviour alterations following chronic neuroleptic administration in mice. J Neural Transm 113:137–150

    PubMed  CAS  Google Scholar 

  89. Fredriksson A, Archer T (2006) Subchronic administration of haloperidol influences the functional deficits of postnatal iron administration in mice. Neurotoxicity Res 10:123–129

    CAS  Google Scholar 

  90. Archer T, Fredriksson A (2006) Influence of noradrenaline denervation on MPTP-induced deficits in mice. J Neural Transm 113:1119–1129

    PubMed  CAS  Google Scholar 

  91. Archer T, Schröder N, Fredriksson A (2003) Neurobehavioural deficits following postnatal iron overload: II Instrumental learning performance. Neurotoxicity Res 5:77–94

    Article  CAS  Google Scholar 

  92. Fredriksson A, Schroder N, Eriksson P, Izquierdo I, Archer T (2000) Maze learning and motor activity deficits in adult mice induced by iron exposure during a critical postnatal period. Brain Res Dev Brain Res 119:65–74

    PubMed  CAS  Google Scholar 

  93. Fredriksson A, Schroder N, Archer T (2003) Neurobehavioural deficits following postnatal iron overload: I spontaneous motor activity. Neurotoxicity Res 5:53–76

    CAS  Google Scholar 

  94. Fredriksson A, Archer T (2002) Functional alteration by NMDA antagonist: effects of L-Dopa, neuroleptics drug and postnatal administration. Amino Acids 23:111–132

    PubMed  CAS  Google Scholar 

  95. Schröder N, Fredriksson A, Vianna MR, Roesler R, Izquierdo I, Archer T (2001) Memory deficits in adult rats following postnatal iron administration. Behav Brain Res 124:77–85

    PubMed  Google Scholar 

  96. Archer T, Palomo T, Fredriksson A (2002) Functional deficits following neonatal dopamine depletion and isolation housing: circular water maze acquisition under pre-exposure conditions and motor activity. Neurotox Res 4:503–522

    PubMed  CAS  Google Scholar 

  97. Ben-Shachar D, Livne E, Spanier I, Zuk R, Youdim MB (1993) Iron modulates neuroleptic-induced effects related to the dopaminergic system. Isr J Med Sci 29:587–592

    PubMed  CAS  Google Scholar 

  98. Yehuda S, Youdim MBH (1989) Brain iron: a lesion from animal models. Am J Clin Nutr 50(Suppl):618–621

    PubMed  CAS  Google Scholar 

  99. Ögren S-O, Archer T (1994) Effects of typical and atypical antipsychotic drugs on two-way active avoidance: relationship to DA receptor blocking profile. Psychopharmacology 114:383–391

    PubMed  Google Scholar 

  100. Richelson E, Elson A (1984) Antagonism of neurotransmitter receptors of normal human brain in vitro. Eur J Pharmacol 103:197–214

    PubMed  CAS  Google Scholar 

  101. Waddington JL (1990) Neuroleptic/dopamine receptors. Eur J Pharmacol 183:106

    Google Scholar 

  102. Meltzer HR, Matsubara S, Lee JC (1989) Classification of typical and atypical antipsychotic drugs on the basis of D1–D2 and serotonin PK1 values. J Pharmacol Exp Ther 251:3238–3246

    Google Scholar 

  103. Berridge CW, Dunn AJ (1990) DSP-4-induced depletion of brain norepinephrine produces opposite effects on exploratory behaviour 3 and 14 days after treatment. Psychopharmacology 100:504–508

    PubMed  CAS  Google Scholar 

  104. Marien MR, Colpaert FC, Rosenquist AC (2004) Noradrenergic mechanisms in neurodegenerative diseases: a theory. Brain Res Rev 45:38–78

    PubMed  CAS  Google Scholar 

  105. Archer T, Bassen M, Peters D, Luthman J, Fredriksson A (1996) Dopaminergic-glutamatergic balance in the forebrain: functional studies of movement disorders in rats and mice. In: Beninger RJ, Palomo T, Archer T (eds) Dopamine disease states. Madrid University Press, Madrid, pp 117–154

    Google Scholar 

  106. Archer T, Fredriksson A (1999) Effects of acute/chronic, subthreshold/threshold doses of L-Dopa in MPTP-treated mice: I influence of competitive and noncompetitive NMDA antagonists. In: Palomo T, Beninger RJ, Archer T (eds) Interactive monoaminergic disorders. Editorial Sintesis, Madrid, pp 573–606

    Google Scholar 

  107. Youdim MBH, Ben-Shachar D, Riederer P (1993) The possible role of iron in the etiopathology of Parkinson’s disease [published erratum appears in Mov Disord 1993 Apr;8(2):255]. Mov Disord 8:1–12

    PubMed  CAS  Google Scholar 

  108. Youdim MBH, Grunblatt E, Mandel S (1999) The pivotal role of iron in NF-kappa B activation and nigrostriatal dopaminergic neurodegeneration. Prospects for neuroprotection in Parkinson’s disease with iron chelators. Ann N Y Acad Sci 890:7–25

    PubMed  CAS  Google Scholar 

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  1. Department of Neuroscience & Psychiatry, Ulleråker, University of Uppsala, Uppsala, 750 17, Sweden

    Trevor Archer

  2. Department of Health and Behavioural Science, Kalmar University, Kalmar, 391, Sweden

    Trevor Archer

  3. Department of Psychology, University of Göteborg, Box 500, Goteborg, 450 30, Sweden

    Trevor Archer & Anders Fredriksson

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Correspondence to Trevor Archer.

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Special issue dedicated to Dr. Moussa Youdim.

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Archer, T., Fredriksson, A. Functional Consequences of Iron Overload in Catecholaminergic Interactions: the Youdim Factor. Neurochem Res 32, 1625–1639 (2007). https://doi.org/10.1007/s11064-007-9358-1

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