Dec 20, 2024

Public workspaceRating of levodopa-induced dyskinesia in 6-OHDA lesioned mice

 Forked from Levodopa-induced dyskinesia mouse model
DOI
https://dx.doi.org/10.17504/protocols.io.5jyl8dm8rg2w/v1
  • Beatriz E Nielson1,
  • Shenyu Zhai2
  • 1University of Colorado Anschutz Medical Campus;
  • 2Northwestern University
Shenyu Zhai
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DOI: https://dx.doi.org/10.17504/protocols.io.5jyl8dm8rg2w/v1
Protocol Citation: Beatriz E Nielson, Shenyu Zhai 2024. Rating of levodopa-induced dyskinesia in 6-OHDA lesioned mice. protocols.io https://dx.doi.org/10.17504/protocols.io.5jyl8dm8rg2w/v1
License: This is an open access protocol distributed under the terms of the Creative Commons Attribution License,  which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Protocol status: Working
We use this protocol and it's working
Created: November 14, 2024
Last Modified: December 20, 2024
Protocol Integer ID: 112128
Keywords: ASAPCRN, induced dyskinesia, behavioral manifestation of levodopa, scoring of abnormal involuntary movement, abnormal involuntary movement, rating of levodopa, levodopa, behavioral manifestation, mice this protocol
Funders Acknowledgements:
Aligning Science Across Parkinson’s (ASAP)
Grant ID: ASAP-020551
Abstract
This protocol describes scoring of abnormal involuntary movements (AIMs), the behavioral manifestation of levodopa-induced dyskinesia, in 6-OHDA lesioned mice.

Materials
Video camera
Clean cage bottoms
L-3,4-Dihydroxyphenylalanine methyl ester hydrochloride (levodopa) (Sigma Aldrich)
Benserazide hydrochloride (Sigma Aldrich)
Sterile insulin syringes
Timer
Troubleshooting
Before start
Generate unilateral 6-OHDA lesioned mice and verify the success of lesioning with the cylinder test.
Dyskinesia: Abnormal Involuntary Movements (AIMs) score
2h 43m
Dyskinesia is assessed using the Abnormal Involuntary Movement score (AIMs) (Cenci and Lundblad, 2007).
Citation
Cenci MA, Lundblad M (2007). Ratings of L-DOPA-induced dyskinesia in the unilateral 6-OHDA lesion model of Parkinson's disease in rats and mice.
https://doi.org/10.1002/0471142301.ns0925s41
LINK
Set up behavior room:
  • Place empty, clean cage bottoms (without bedding material) with at least 30 cm in between.
  • Set up video camera.
Habituate the mice by bringing their home cage(s) to the behavior room and leaving it undisturbed for at least 30 minutes.
Prepare fresh levodopa solution by dissolving 6 mg or 12 mg levodopa (L-3,4-Dihydroxyphenylalanine methyl ester hydrochloride) and 12 mg benserazide hydrochloride in 10 ml sterile saline. This solution is to be used within 40 min.
Weigh the first mouse.
Perform intraperitoneal (i.p.) injection of levodopa (6.0 mg/kg for the first two sessions and 12.0 mg/kg for later sessions) plus 12 mg/kg of benserazide in the first mouse. Place the mouse in a clean cage bottom labeled with its ID. Start the timer.
1m
After 1 min, inject the second mouse and place it in its labeled cage bottom. Repeat until all mice are injected.

Duration00:20:00 after the first injection, videotape and score the first mouse for Duration00:01:00 . Repeat for all the mice.
Score for each of the three body segments: axial, limb, and orolingual AIMs. The AIM scale ranges from 0 to 4 for each body segment during a 1-minute period.
For each segment:
  • 0 = normal movement.
  • 1 = abnormal movement for <50% of the time.
  • 2 = abnormal movement for >50% of the time.
  • 3 = abnormal movement for the entire period but can be interrupted by external stimuli (e.g. tapping on the cage wall).
  • 4 = continuous, unsuppressible abnormal movement.
Half scores (e.g. 1.5, 2.5, 3.5) are possible.
21m
Repeat Step 8 every Duration00:20:00 for a total period of Duration02:00:00 (There must be videos recorded at 20 min, 40 min, 60 min, 80 min, 100 min and 120 min time points for each mouse).

2h 20m
Return the mice to their home cage(s).
AIM scoring is performed every other day for a total of five sessions.
Protocol references
Cenci, M.A. & Lundblad, M. Ratings of L-DOPA-induced dyskinesia in the unilateral 6-OHDA lesion model of Parkinson's disease in rats and mice. Curr Protoc Neurosci Chapter 9, Unit 9 25, doi:10.1002/0471142301.ns0925s41 (2007).

Fieblinger, T. et al. Cell type-specific plasticity of striatal projection neurons in parkinsonism and L-DOPA-induced dyskinesia. Nat Commun 5, 5316, doi:10.1038/ncomms6316 (2014).

Shen, W. X. et al. M4 Muscarinic Receptor Signaling Ameliorates Striatal Plasticity Deficits in Models of L DOPA-Induced Dyskinesia (vol 88, pg 762, 2015). Neuron 90, 1139-1139, doi:10.1016/j.neuron.2016.05.017 (2016).
Citations
Step 1
Cenci MA, Lundblad M. Ratings of L-DOPA-induced dyskinesia in the unilateral 6-OHDA lesion model of Parkinson's disease in rats and mice.
https://doi.org/10.1002/0471142301.ns0925s41