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

Breger, Ludivine S LU ; Dunnett, Stephen B and Lane, Emma L LU (2013) In Neurobiology of Disease 50. p.50-142
Abstract

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... (More)

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.

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author
publishing date
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Contribution to journal
publication status
published
keywords
Adrenergic Agents, Amantadine, Animals, Antiparkinson Agents, Dopamine Agonists, Dyskinesia, Drug-Induced, Levodopa, Oxidopamine, Parkinsonian Disorders, Rats, Rats, Sprague-Dawley, Severity of Illness Index, Comparative Study
in
Neurobiology of Disease
volume
50
pages
9 pages
publisher
Elsevier
external identifiers
  • Scopus:84868462682
ISSN
0969-9961
DOI
10.1016/j.nbd.2012.10.013
language
English
LU publication?
no
id
10e7505f-8c15-42dc-8db6-0b4ab5adc5a8
date added to LUP
2016-10-04 13:20:19
date last changed
2016-10-13 05:14:39
@misc{10e7505f-8c15-42dc-8db6-0b4ab5adc5a8,
  abstract     = {<p>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.</p>},
  author       = {Breger, Ludivine S and Dunnett, Stephen B and Lane, Emma L},
  issn         = {0969-9961},
  keyword      = {Adrenergic Agents,Amantadine,Animals,Antiparkinson Agents,Dopamine Agonists,Dyskinesia, Drug-Induced,Levodopa,Oxidopamine,Parkinsonian Disorders,Rats,Rats, Sprague-Dawley,Severity of Illness Index,Comparative Study},
  language     = {eng},
  pages        = {50--142},
  publisher    = {ARRAY(0x8b52bf0)},
  series       = {Neurobiology of Disease},
  title        = {Comparison of rating scales used to evaluate L-DOPA-induced dyskinesia in the 6-OHDA lesioned rat},
  url          = {http://dx.doi.org/10.1016/j.nbd.2012.10.013},
  volume       = {50},
  year         = {2013},
}