Comparison of rating scales used to evaluate L-DOPA-induced dyskinesia in the 6-OHDA lesioned rat

LS Breger, SB Dunnett, EL Lane - Neurobiology of disease, 2013 - Elsevier
LS Breger, SB Dunnett, EL Lane
Neurobiology of disease, 2013Elsevier
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 …
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 6mg/kg/day for 5weeks followed by 12mg/kg/day for another 5weeks. Rats were assessed weekly by simultaneous ratings on four published AIM and stereotypy scales with concurrent recording of rotation, over 3hours 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 D1 and D2 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.
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