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Spatial deficits in a mouse model of Parkinson disease

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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.

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Acknowledgments

The authors would like to thank Dr. Arianna Rinaldi for her assistance with the TH staining. The present study has been supported by a Galileo grant (to A.M. and M.A.), P.R.I.N. and F.I.R.B. grants from M.I.U.R. to A.O. to A.M. and a D.C.M.C grant from A.S.I. to A.O. and A.M. Every possible effort was made to minimize animal suffering, and all procedures were in strict accordance with the European Communities Council directives (86/609/EEC) and regulations on the use of animals in research and NIH guidelines on animal care.

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Authors and Affiliations

  1. Dipartimento di Genetica e Biologia Molecolare “C.Darwin”, Università degli Studi di Roma “La Sapienza”, Piazzale Aldo Moro, 5, Rome, Italy

    Elvira De Leonibus, Alberto Oliverio & Andrea Mele

  2. Centro di Ricerca in Neurobiologia-D. Bovet, Università degli Studi di Roma “La Sapienza”, Rome, Italy

    Elvira De Leonibus, Tiziana Pascucci, Alberto Oliverio & Andrea Mele

  3. IRCCS, Fondazione Santa Lucia, Rome, Italy

    Tiziana Pascucci

  4. Laboratoire de Neurobiologie de la Cognition, Universités Aix-Marseille, CNRS UMR6155, Marseille, France

    Sebastien Lopez & Marianne Amalric

  5. Istituto di Neuroscienze-CNR, CERC, Rome, Italy

    Alberto Oliverio & Andrea Mele

Authors
  1. Elvira De Leonibus
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  2. Tiziana Pascucci
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  3. Sebastien Lopez
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  4. Alberto Oliverio
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  5. Marianne Amalric
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  6. Andrea Mele
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Corresponding author

Correspondence to Elvira De Leonibus.

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De Leonibus, E., Pascucci, T., Lopez, S. et al. Spatial deficits in a mouse model of Parkinson disease. Psychopharmacology 194, 517–525 (2007). https://doi.org/10.1007/s00213-007-0862-4

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  • DOI: https://doi.org/10.1007/s00213-007-0862-4

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