The Rodent Models of Dyskinesia and Their Behavioral Assessment

Abstract

Dyskinesia, a major motor complication resulting from dopamine replacement treatment, manifests as involuntary hyperkinetic or dystonic movements. This condition poses a challenge to the treatment of Parkinson's disease. So far, several behavioral models based on rodent with dyskinesia have been established. These models have provided an important platform for evaluating the curative effect of drugs at the preclinical research level over the past two decades. However, there are differences in the modeling and behavioral testing procedures among various laboratories that adversely affect the rat and mouse models as credible experimental tools in this field. This article systematically reviews the history, the pros and cons, and the controversies surrounding rodent models of dyskinesia as well as their behavioral assessment protocols. A summary of factors that influence the behavioral assessment in the rodent dyskinesia models is also presented, including the degree of dopamine denervation, stereotaxic lesion sites, drug regimen, monitoring styles, priming effect, and individual and strain differences. Besides, recent breakthroughs like the genetic mouse models and the bilateral intoxication models for dyskinesia are also discussed.

PET Imaging of the Adenosine A2A Receptor in the Rotenone-Based Mouse Model of Parkinson’s Disease with [18F]FESCH Synthesized by a Simplified Two-Step One-Pot Radiolabeling Strategy

“…In the rotenone-treated mice, we did not identify any signs of dyskinesia and, thus, it is not surprising that in this PD mouse model no significant increase in the A 2A R density was detected either by PET imaging or by immunofluorescence staining. With regard to dyskinesia, the rotenone model is comparable to another neurotoxin-based PD mouse model using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), where only weak signs of dyskinesia were observed and this exclusively under L-DOPA treatment [42]. To date, unilateral injection of 6-hydroxydopamine (6-OHDA) is the only effective neurotoxin-related approach to replicate evidently some forms of dyskinesia in rats and mice.…”

“…To date, unilateral injection of 6-hydroxydopamine (6-OHDA) is the only effective neurotoxin-related approach to replicate evidently some forms of dyskinesia in rats and mice. In the 6-OHDA mouse model, dyskinesia is detected as abnormal involuntary movements (AIMs) with a more simplified range than in rats, presenting more prominent rotational locomotion with less dystonic features, i.e., axial AIMs [42]. None of the above-mentioned AIMs were detected in the rotenone-treated mice.…”

Neuronal mechanism of a BK channelopathy in absence epilepsy and movement disorders

“…This discrepancy is likely due to the organism difference between mice and humans. It is also possible that the frequent absence seizures in the BK-D434G mice complicate the detection of PNKD, which is not trivial to monitor in mouse models (52). Nevertheless, the hyperexcitability and morphological changes of the BK-D434G Purkinje cells explicitly demonstrated the involvement of the cerebellum in the pathogenesis of PNKD.…”

Continuous long-range measurement of tonic dopamine with advanced FSCV for pharmacodynamic analysis of levodopa-induced dyskinesia in Parkinson’s disease

“…To assess dyskinetic behaviors immediately after acute levodopa administration, we employed the rotational behavior, which is evident in hemi-PD model mice. Rotational behavior is a one of dyskinetic response that correlates with other rodent dyskinetic parameters in the hemi-PD model ( Henry et al, 1998 ; Konitsiotis and Tsironis, 2006 ; Peng et al, 2019 ), resulting from DA imbalance between the left and right hemispheres. Contraversive rotation in the hemi-PD model reflects the severity of the dyskinetic response over time following levodopa administration.…”