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

Breger, Ludivine S., Dunnett, Stephen Bruce ORCID: https://orcid.org/0000-0003-1826-1578 and Lane, Emma Louise ORCID: https://orcid.org/0000-0001-8800-3764 2013. Comparison of rating scales used to evaluate l-DOPA-induced dyskinesia in the 6-OHDA lesioned rat. Neurobiology of Disease 50 , pp. 142-150. 10.1016/j.nbd.2012.10.013

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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 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 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences Pharmacy
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry R Medicine > RS Pharmacy and materia medica
Uncontrolled Keywords:	Parkinson disease; Rodent; LID; AIM; Rotation; Stereotypy
Publisher:	Elsevier
ISSN:	0969-9961
Last Modified:	09 Nov 2022 07:58
URI:	https://orca.cardiff.ac.uk/id/eprint/41683

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