Comparison of rating scales used to evaluate L-DOPA-induced dyskinesia in the 6-OHDA lesioned rat.
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.
School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, CF10 3NB, UK. bregerLS@cardiff.ac.uk
Ludivine S
LS
Breger
Stephen B
SB
Dunnett
Emma L
EL
Lane
D018663:Adrenergic Agents / Q000633:toxicity; D000547:Amantadine / Q000494:pharmacology; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D018491:Dopamine Agonists / Q000009:adverse effects*; D004409:Dyskinesia, Drug-Induced / Q000175:diagnosis*; D007980:Levodopa / Q000009:adverse effects*; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index
D018663:Adrenergic Agents; D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D007980:Levodopa; D016627:Oxidopamine; D000547:Amantadine