title: Functional consequences of iron overload in catecholaminergic interactions: the Youdim factor.
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 D(2) 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.
authors: Department of Neuroscience & Psychiatry, Ulleråker, University of Uppsala, Uppsala, 750 17, Sweden. Trevor.Archer@psy.gu.se
authors: Trevor
authors: T
authors: Archer
authors: Anders
authors: A
authors: Fredriksson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D014150:Antipsychotic Agents / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002395:Catecholamines / Q000502:physiology*; D003024:Clozapine / Q000494:pharmacology; D003714:Denervation; D004298:Dopamine / Q000502:physiology; D015259:Dopamine Agents / Q000494:pharmacology; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000503:physiopathology* / Q000523:psychology*; D007980:Levodopa / Q000494:pharmacology; D020267:MPTP Poisoning / Q000378:metabolism / Q000523:psychology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D009069:Movement Disorders / Q000503:physiopathology; D009638:Norepinephrine / Q000502:physiology; D011247:Pregnancy; D011618:Psychotic Disorders / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology; D015430:Weight Gain / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D002395:Catecholamines; D015259:Dopamine Agents; D007980:Levodopa; D007501:Iron; D003024:Clozapine; D006220:Haloperidol; D004298:Dopamine; D009638:Norepinephrine
references: Eur J Pharmacol. 1991 Sep 17;202(2):177-83
references: 1687031
references: J Neural Transm Suppl. 1995;46:157-64
references: 8821051
references: Isr J Med Sci. 1993 Sep;29(9):587-92
references: 7901181
references: Radiology. 1986 May;159(2):493-8
references: 3961182
references: J Comp Physiol Psychol. 1982 Jun;96(3):491-516
references: 7096685
references: Eur J Pharmacol. 1981 Jun 19;72(2-3):173-88
references: 6265244
references: Eur J Pharmacol. 1993 Jun 4;236(3):487-9
references: 7689466
references: Mol Chem Neuropathol. 1989 Jun;10(3):171-83
references: 2669769
references: Lancet. 1987 Nov 21;2(8569):1219-20
references: 2890848
references: Am J Clin Nutr. 1989 Sep;50(3 Suppl):618-25; discussion 625-9
references: 2570524
references: Pharmacol Toxicol. 1990 Oct;67(4):295-301
references: 2077520
references: Neurotox Res. 2003;5(1-2):77-94
references: 14628858
references: Neurotox Res. 2000 Apr;1(4):249-59
references: 12835093
references: J Neural Transm (Vienna). 2006 Feb;113(2):137-50
references: 16082515
references: Psychopharmacology (Berl). 1983;81(1):1-5
references: 6415724
references: Ann N Y Acad Sci. 2004 Mar;1012:306-25
references: 15105275
references: Behav Brain Res. 2003 Feb 17;139(1-2):31-46
references: 12642174
references: Neuroscience. 1983 Aug;9(4):889-98
references: 6312376
references: J Pharmacol Exp Ther. 1981 Dec;219(3):695-700
references: 7197719
references: Brain Res Brain Res Rev. 2004 Apr;45(1):38-78
references: 15063099
references: J Neural Transm (Vienna). 2004 Oct;111(10-11):1455-71
references: 15480846
references: Life Sci. 1981 Sep 28;29(13):1341-6
references: 7197320
references: Amino Acids. 2002;23(1-3):111-32
references: 12373526
references: Psychopharmacology (Berl). 1990;100(4):504-8
references: 2320711
references: Ann Clin Psychiatry. 2003 Mar;15(1):33-48
references: 12839431
references: Behav Neural Biol. 1985 May;43(3):238-49
references: 3842248
references: Neurotox Res. 2000 Apr;1(4):235-47
references: 12835092
references: Eur J Pharmacol. 1976 Oct;39(2):275-82
references: 185062
references: Nutrition. 2000 Jul-Aug;16(7-8):504-8
references: 10906537
references: Behav Brain Res. 2001 Sep 28;124(1):77-85
references: 11423168
references: Exp Neurol. 1991 Oct;114(1):73-81
references: 1915737
references: Neuroscience. 1982;7(11):2895-907
references: 7155358
references: Science. 1969 Oct 31;166(3905):635-7
references: 5823302
references: J Pharm Pharmacol. 1976 May;28(5):458-9
references: 6763
references: Brain Res Dev Brain Res. 1990 Aug 1;55(1):35-42
references: 2208639
references: Med Biol. 1981 Jun;59(3):161-9
references: 6796787
references: Eur J Pharmacol. 1970;11(3):315-20
references: 5477308
references: J Neurochem. 2005 Oct;95(1):68-78
references: 16181413
references: Neuropharmacology. 1974 Nov;13(10-11):927-40
references: 4474641
references: Toxicol Appl Pharmacol. 1999 Aug 15;159(1):25-30
references: 10448122
references: J Neurochem. 1991 Nov;57(5):1584-92
references: 1919575
references: J Neurochem. 1990 Apr;54(4):1136-41
references: 1968955
references: Br J Pharmacol. 1976 Dec;58(4):521-7
references: 1000130
references: Brain Res. 1990 Jun 4;518(1-2):31-9
references: 2390723
references: Psychopharmacology (Berl). 1994 Apr;114(3):383-91
references: 7855196
references: Eur J Pharmacol. 1993 Nov 2;249(1):37-41
references: 7506666
references: Bioorg Med Chem. 2005 Feb 1;13(3):773-83
references: 15653345
references: Neurosci Lett. 1991 Feb 25;123(2):244-7
references: 2027538
references: J Neural Transm Gen Sect. 1992;87(3):225-30
references: 1533773
references: Eur J Pharmacol. 1985 Jul 17;113(2):159-65
references: 2864265
references: J Pharmacol Exp Ther. 1975 Apr;193(1):88-94
references: 166158
references: Mov Disord. 1993;8(1):1-12
references: 8419792
references: Psychopharmacology (Berl). 1982;76(4):303-9
references: 6812102
references: Pharmacol Biochem Behav. 1983 Jul;19(1):121-30
references: 6684774
references: Brain Res Dev Brain Res. 2000 Jan 3;119(1):65-74
references: 10648873
references: J Neurol Sci. 1995 Dec;134 Suppl:69-78
references: 8847547
references: Life Sci. 1985 Jan 21;36(3):201-6
references: 2857048
references: J Neural Transm (Vienna). 2003 Feb;110(2):183-200
references: 12589577
references: J Pharmacol Exp Ther. 1997 Oct;283(1):100-7
references: 9336313
references: Eur Neurol. 1991;31 Suppl 1:34-40
references: 1649757
references: Pharmacol Biochem Behav. 1986 Jul;25(1):141-4
references: 3018790
references: Brain Res. 1990 Oct 1;528(2):181-8
references: 2271921
references: Eur J Pharmacol. 1986 Oct 7;129(3):339-45
references: 3490988
references: Naunyn Schmiedebergs Arch Pharmacol. 1977 Jan;296(2):183-5
references: 834317
references: Eur J Pharmacol. 1983 Apr 22;89(1-2):27-33
references: 6861888
references: Bibl Anat. 1982;(23 ):76-92
references: 6291505
references: J Neurochem. 1989 Feb;52(2):515-20
references: 2911028
references: Eur J Pharmacol. 1984 Aug 17;103(3-4):197-204
references: 6149136
references: Eur J Pharmacol. 1977 Dec 15;46(4):363-9
references: 590344
references: Parkinsonism Relat Disord. 2001 Apr;7(2):97-105
references: 11248590
references: J Neurochem. 1958 Oct;3(1):41-51
references: 13611557
references: Neurotox Res. 2003;5(1-2):53-76
references: 14628856
references: Arch Neurol. 1991 Dec;48(12):1285-93
references: 1845035
references: Psychopharmacology (Berl). 1986;88(2):141-6
references: 3081924
references: J Neural Transm Park Dis Dement Sect. 1994;7(2):123-32
references: 7710664
references: Neurotox Res. 2001 Oct;3(5):411-32
references: 14715456
references: Neurotox Res. 2002 Aug-Sep;4(5-6):503-522
references: 12754163
references: Neurol Clin. 1992 May;10(2):405-20
references: 1584182
references: Eur J Pharmacol. 1987 May 7;137(1):107-16
references: 2886347
references: J Neurochem. 1966 Aug;13(8):655-69
references: 5950056
references: J Pharmacol Exp Ther. 1989 Oct;251(1):238-46
references: 2571717
references: Eur J Pharmacol. 1986 Jan 29;120(3):295-307
references: 3081358
references: Neurotox Res. 2006 Oct;10(2):123-9
references: 17062374
references: Br Med Bull. 1993 Jul;49(3):577-87
references: 8221024
references: J Med Chem. 1995 Jan 6;38(1):150-60
references: 7530773
references: J Neurochem. 1994 Sep;63(3):793-807
references: 7519659
references: J Neural Transm (Vienna). 1999;106(3-4):283-300
references: 10392537
references: Life Sci. 1985 Oct 14;37(15):1419-23
references: 4046742
references: J Pharmacol Exp Ther. 1991 Jul 1;258(1):58-65
references: 1830099
references: J Neural Transm (Vienna). 2006 Sep;113(9):1119-29
references: 16362627
references: Brain. 1991 Aug;114 ( Pt 4):1953-75
references: 1832073
references: Br J Pharmacol. 1984 May;82(1):249-57
references: 6733355
references: J Clin Psychiatry. 1998;59 Suppl 3:38-43
references: 9541337
references: Nat Rev Neurosci. 2004 Nov;5(11):863-73
references: 15496864
references: Neurodegeneration. 1996 Sep;5(3):241-9
references: 8910902
references: Ann N Y Acad Sci. 1999;890:7-25
references: 10668410