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.
OBJECTIVE
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.


METHODS
Rats were given mild or severe unilateral 6-OHDA lesions, scanned with the tracer [(11)C](+/-)dihydrotetrabenazine ([(11)C]DTBZ), and tested on a tapered/ledged beam-walking task. At postmortem, autoradiography was performed with [(11)C]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.
Strome
Elissa M
EM
Pacific Parkinson's Research Centre, University of British Columbia, Purdy Pavilion M36, 2221 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada. strome@interchange.ubc.ca
Cepeda
Ivan L
IL
Sossi
Vesna
V
Doudet
Doris J
DJ
D000818:Animals; D001345:Autoradiography / Q000379:methods; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects; D002250:Carbon Radioisotopes; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D023421:Models, Animal; D009043:Motor Activity; D016627:Oxidopamine / Q000009:adverse effects; D010300:Parkinson Disease / Q000000981:diagnostic imaging*; D010865:Pilot Projects; D049268:Positron-Emission Tomography / Q000379:methods; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D013747:Tetrabenazine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; C032811:dihydrotetrabenazine; D016627:Oxidopamine; D004298:Dopamine; D013747:Tetrabenazine