Psychopharmacology

, Volume 194, Issue 4, pp 517–525 | Cite as

Spatial deficits in a mouse model of Parkinson disease

  • Elvira De Leonibus
  • Tiziana Pascucci
  • Sebastien Lopez
  • Alberto Oliverio
  • Marianne Amalric
  • Andrea Mele
Original Investigation

Abstract

Rationale

Accumulating evidence in humans demonstrated that visuo-spatial deficits are the most consistently reported cognitive abnormalities in Parkinson disease (PD). These deficits have been generally attributed to cortical dopamine degeneration. However, more recent evidence suggests that dopamine loss in the striatum is responsible for the visuo-spatial abnormalities in PD. Studies based on animal models of PD did not specifically address this question.

Objectives

Thus, the first goal of this study was to analyze the role of dopamine within the dorsal striatum in spatial memory. We tested bilateral 6-OHDA striatal lesioned CD1 mice in an object–place association spatial task. Furthermore, to see whether the effects were selective for spatial information, we measured how the 6-OHDA-lesioned animals responded to a non-spatial change and learned in the one-trial inhibitory avoidance task.

Results

The results demonstrated that bilateral (approximately 75%) dopamine depletion of the striatum impaired spatial change discrimination. On the contrary, no effect of the lesion was observed on non-spatial novelty detection or on passive avoidance learning.

Conclusions

These results confirm that dopamine depletion is accompanied by cognitive deficits and demonstrate that striatal dopamine dysfunction is sufficient to induce spatial information processing deficits.

Keywords

Mice Dopamine Spatial memory 6-Hydroxydopamine Passive avoidance Dorsal striatum Parkinson disease Cognitive deficits Novel object task Working memory 

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Elvira De Leonibus
    • 1
    • 2
  • Tiziana Pascucci
    • 2
    • 3
  • Sebastien Lopez
    • 4
  • Alberto Oliverio
    • 1
    • 2
    • 5
  • Marianne Amalric
    • 4
  • Andrea Mele
    • 1
    • 2
    • 5
  1. 1.Dipartimento di Genetica e Biologia Molecolare “C.Darwin”Università degli Studi di Roma “La Sapienza”RomeItaly
  2. 2.Centro di Ricerca in Neurobiologia-D. BovetUniversità degli Studi di Roma “La Sapienza”RomeItaly
  3. 3.IRCCSFondazione Santa LuciaRomeItaly
  4. 4.Laboratoire de Neurobiologie de la CognitionUniversités Aix-MarseilleMarseilleFrance
  5. 5.Istituto di Neuroscienze-CNRCERCRomeItaly

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