Comparison of rating scales used to evaluate L-DOPA-induced dyskinesia in the 6-OHDA lesioned rat.
Neurobiology of Disease. 2013-02-01; 50: 142-150
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1. Neurobiol Dis. 2013 Feb;50:142-50. doi: 10.1016/j.nbd.2012.10.013. Epub 2012 Oct
Comparison of rating scales used to evaluate L-DOPA-induced dyskinesia in the
6-OHDA lesioned rat.
Breger LS(1), Dunnett SB, Lane EL.
(1)School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff,
CF10 3NB, UK.
Abnormal involuntary movement (AIM) rating scales are frequently used to study
the mechanisms underlying L-DOPA-induced dyskinesia (LID) in 6-OHDA lesioned
rodents and the propensity of novel treatments for Parkinson’s disease to induce
or alleviate similar abnormal behaviours. Despite the existence of at least one
well validated method, other AIM scales are also in use. Moreover, there have
been developments and variations in the original scales and their methods of use,
without re-validation. In this study, 6-OHDA medial forebrain bundle lesioned
Sprague-Dawley rats were treated with chronic L-DOPA 6 mg/kg/day for 5 weeks
followed by 12 mg/kg/day for another 5 weeks. Rats were assessed weekly by
simultaneous ratings on four published AIM and stereotypy scales with concurrent
recording of rotation, over 3 hours following L-DOPA injection. Three
contemporary AIM scales have then been validated pharmacologically using agents
that are known to reduce LID clinically and in primates (amantadine) or to
interfere with the activity of L-DOPA (the D(1) and D(2) dopamine receptor
antagonists, SCH-23390 and raclopride) respectively. We also demonstrate that
AIM, stereotypic and rotational behaviour are distinct motor dysfunctions induced
by chronic and acute treatment of L-DOPA, and should be assessed separately. The
undertaking of assessments at multiple time points is essential especially when
testing the efficacy of new potential anti-dyskinetic treatments. Importantly
critical to all AIM and rotation testing is the internal validation of both the
scale being used and the environment being used.
Copyright © 2012 Elsevier Inc. All rights reserved.
PMID: 23072976 [Indexed for MEDLINE]