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

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.