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Evaluation of the Integrity of the Dopamine System in a Rodent Model of Parkinson’s Disease: Small Animal Positron Emission Tomography Compared to Behavioral Assessment and Autoradiography

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Abstract

Purpose

In the 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease (PD), it is important to determine lesion severity. This evaluation can be performed in vivo, through evaluation of dopamine (DA)-dependent motor function or with small animal positron emission tomography (microPET), or at postmortem, by examining markers for DA neurons.

Procedures

Rats were given mild or severe unilateral 6-OHDA lesions, scanned with the tracer [11C](±)dihydrotetrabenazine ([11C]DTBZ), and tested on a tapered/ledged beam-walking task. At postmortem, autoradiography was performed with [11C]DTBZ.

Results

Autoradiography was significantly correlated with microPET and behavioral scores, whereas the microPET and behavioral data were not significantly correlated.

Conclusions

This study shows that behavioral analysis, microPET, and autoradiography are all good tools for measuring the integrity of the DA system, and demonstrates the utility of the tapered/ledged beam-walking test to screen for lesion severity, as well as the importance of including postmortem analysis after in vivo imaging studies.

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Acknowledgments

We are grateful for technical assistance from Siobhan McCormick (microPET technician), Rick Kornelsen, and Jessica Grant (animal technicians), and to the staff at the UBC Animal Resource Unit. The authors would also like to acknowledge the staff of the UBC/TRIUMF PET group, and in particular Dr. Tom Ruth (Head), for their support of these studies. This work was supported by The Canadian Foundation for Innovation, The Canadian Institutes of Health Research, and the Michael Smith Foundation for Health Research. A version of this work was presented at the Academy of Molecular Imaging 2005 Annual Meeting, Orlando, FL.

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Authors and Affiliations

  1. Pacific Parkinson’s Research Centre, University of British Columbia, Purdy Pavilion M36, 2221 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada

    Elissa M. Strome, Ivan L. Cepeda, Vesna Sossi & Doris J. Doudet

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  1. Elissa M. Strome
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  2. Ivan L. Cepeda
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  3. Vesna Sossi
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  4. Doris J. Doudet
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Correspondence to Elissa M. Strome.

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Strome, E.M., Cepeda, I.L., Sossi, V. et al. Evaluation of the Integrity of the Dopamine System in a Rodent Model of Parkinson’s Disease: Small Animal Positron Emission Tomography Compared to Behavioral Assessment and Autoradiography. Mol Imaging Biol 8, 292–299 (2006). https://doi.org/10.1007/s11307-006-0051-6

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