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Neurotoxin Modeling of Brain Disorders—Life-long Outcomes in Behavioral Teratology pp 73–86Cite as

Noradrenergic–Dopaminergic Interactions Due to DSP-4–MPTP Neurotoxin Treatments: Iron Connection

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Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 29))

Abstract

The investigations of noradrenergic lesions and dopaminergic lesions have established particular profiles of functional deficits and accompanying alterations of biomarkers in brain regions and circuits. In the present account, the focus of these lesions is directed toward the effects upon dopaminergic neurotransmission and expression that are associated with the movement disorders and psychosis-like behavior. In this context, it was established that noradrenergic denervation, through administration of the selective noradrenaline (NA) neurotoxin, DSP-4, should be performed prior to the depletion of dopamine (DA) with the selective neurotoxin, MPTP. Employing this regime, it was shown that (i) following DSP-4 (50 mg/kg) pretreatment of C57/Bl6 mice, both the functional and neurochemical (DA loss) effects of MPTP (2 × 20 and 2 × 40 mg/kg) were markedly exacerbated, and (ii) following postnatal iron (Fe2+, 7.5 mg/kg, on postnatal days 19–12), pretreatment with DSP-4 followed by the lower 2 × 20 mg/kg MPTP dose induced even greater losses of motor behavior and striatal DA. As yet, the combination of NA-DA depletions, and even more so Fe2+–NA-DA depletion, has been considered to present a movement disorder aspect although studies exploring cognitive domains are lacking. With intrusion of iron overload into this formula, the likelihood of neuropsychiatric disorder, as well, unfolds.

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  1. Department of Psychology, University of Gothenburg, Gothenburg, Sweden

    Trevor Archer

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  1. Department of Biomedical Sciences, East Tennessee State University, Johnson City, TN, USA

    Richard M. Kostrzewa

  2. Department of Psychology, University of Gothenburg, Gothenburg, Sweden

    Trevor Archer

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Archer, T. (2015). Noradrenergic–Dopaminergic Interactions Due to DSP-4–MPTP Neurotoxin Treatments: Iron Connection. In: Kostrzewa, R.M., Archer, T. (eds) Neurotoxin Modeling of Brain Disorders—Life-long Outcomes in Behavioral Teratology. Current Topics in Behavioral Neurosciences, vol 29. Springer, Cham. https://doi.org/10.1007/7854_2015_411

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