Original Paper

Neurochemical Research

, Volume 32, Issue 10, pp 1625-1639

First online:

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

  • Trevor ArcherAffiliated withDepartment of Neuroscience & Psychiatry, Ulleråker, University of UppsalaDepartment of Health and Behavioural Science, Kalmar UniversityDepartment of Psychology, University of Göteborg Email author 
  • , Anders FredrikssonAffiliated withDepartment of Psychology, University of Göteborg

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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.


Iron administration Postnatal Fe2+ Vehicle Clozapine Haloperidol Basal ganglia Motor deficits Locomotion Rearing Total activity DA D2 receptor supersensitivity Behavioural deficits