How reliable is the behavioural evaluation of dyskinesia in animal models of Parkinson's disease?
In spite of the current availability of several pharmacological therapies for the treatment of Parkinson's disease, side effects are invariably manifested during long-term treatment. Dyskinesia, wearing-off and on-off are among the most disabling side effects produced by the dopamine precursor L-dihydroxyphenylalanine and, to a lesser degree, by other pharmacological treatments based on dopamine receptor agonism. Evaluation of the side effects, in particular dyskinesia, produced by antiparkinsonian drug treatments, therefore represents a critical issue in drug validation prior to a clinical trial. Moreover, a reliable model of dyskinesia is a fundamental requirement for the study of the as yet unknown mechanisms at the basis of this severely disabling side effect. The present review aims to provide a critical evaluation of the validity, reliability and utility of animal models of dyskinesia. In the first part of this review, we present a brief overview of the different models of Parkinson's disease focusing on those utilized for the evaluation of dyskinetic movements, then proceed to critically examine the turning behaviour model in an attempt to assess the way in which it has influenced the evaluation of drugs utilized in the treatment of Parkinson's disease. Subsequently, the various models of dyskinesia are reviewed and conclusions are drawn as to how the environment in which experiments are performed can influence the behaviour observed.
Carta
Anna R
AR
Department of Toxicology and Centre of Excellence for Neurobiology of Dependence, University of Cagliari bCNR Institute for Neuroscience - Section of Cagliari, Cagliari, Italy.
Pinna
Annalisa
A
Morelli
Micaela
M
D000818:Animals; D000978:Antiparkinson Agents / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects*; D015259:Dopamine Agents / Q000633:toxicity; D004353:Drug Evaluation, Preclinical; D004409:Dyskinesia, Drug-Induced / Q000209:etiology*; D007980:Levodopa / Q000633:toxicity; D009043:Motor Activity / Q000187:drug effects; D009048:Motor Skills / Q000187:drug effects; D020734:Parkinsonian Disorders / Q000188:drug therapy*; D013239:Stereotyped Behavior / Q000187:drug effects
D000978:Antiparkinson Agents; D015259:Dopamine Agents; D007980:Levodopa