Journal of Neural Transmission

, Volume 113, Issue 9, pp 1119–1129 | Cite as

Influence of noradrenaline denervation on MPTP-induced deficits in mice

  • T. Archer
  • A. Fredriksson


C57/BL6 mice were administered either DSP4 (50 mg/kg, s.c., 30 min after injection of zimeldine, 20 mg/kg, s.c.) or vehicle (saline) at 63 days of age. Three weeks later, one group (n = 10) of DSP4-treated and one group of vehicle-treated mice were administered MPTP (2 × 40 mg/kg, s.c., 24 hours between injections; the High dose groups), one group (n = 10) of DSP4-treated and one group of vehicle-treated mice were administered MPTP (2 × 20 mg/kg, s.c., 24 hours between injections; the Low dose groups), and one group (n = 10) of DSP4-treated and one group of vehicle-treated mice were administered vehicle. Three weeks later, all six groups were tested in motor activity test chambers, followed by injections of L-Dopa (20 mg/kg, s.c.), and then tested over a further 360 min in the activity test chambers. It was found that pretreatment with the selective NA neurotoxin, DSP4, deteriorated markedly the dose-dependent motor activity deficits observed in the vehicle pretreated MPTP treated mice. These ‘ultra-deficits’ in the spontaneous motor behaviour of MPTP-treated mice were observed over all three parameters: locomotion, rearing and total activity, and were restricted to the 1st and 2nd 20-min periods. Administration of L-Dopa (20 mg/kg) following the 60-min testing of spontaneous behaviour restored the motor activity of Vehicle + MPTP treated mice (neither the Vehicle + MPTP-Low nor the Vehicle + MPTP-High groups differed from the Vehicle–Vehicle group, here) but failed to do so in the DSP4 pretreated mice. Here, a dose-dependent deficit of L-Dopa-induced motor activity (over all three parameters) was obtained thereby offering further evidence of an ‘ultra-deficit’ of function due to previous denervation of the NA terminals. The present findings support the notion that severe damage to the locus coeruleus noradrenergic system, through systemic DSP4, disrupts the facilitatory influence on the nigrostriatal DA system, and interferes with the ability of the nigrostriatal pathway to compensate for or recover from marked injury, MPTP treatment.

Keywords: DSP4, MPTP, vehicle, motor deficits, locomotion, rearing, total activity, L-Dopa, restoration, attenuation, DA, NA, C57/BL6 mice, movement disorder, PD. 


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • T. Archer
    • 1
    • 2
  • A. Fredriksson
    • 3
  1. 1.Department of PsychologyUniversity of GöteborgGöteborgSweden
  2. 2.Department of Health and Behavioural ScienceKalmar UniversityKalmarSweden
  3. 3.Department of NeurosciencePsychiatry Ulleråker, University of UppsalaUppsalaSweden

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