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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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