Animal models of l-DOPA-induced dyskinesia: the 6-OHDA-lesioned rat and mouse

Research output: Contribution to journalArticle

Abstract

Appearance of l-DOPA-induced dyskinesia (LID) represents a major limitation in the pharmacological therapy with the dopamine precursor l-DOPA. Indeed, the vast majority of parkinsonian patients develop dyskinesia within 9–10 years of l-DOPA oral administration. This makes the discovery of new therapeutic strategies an important need. In the last decades, several animal models of Parkinson’s disease (PD) have been developed, to both study mechanisms underlying PD pathology and treatment-induced side effects (i.e., LID) and to screen for new potential anti-parkinsonian and anti-dyskinetic treatments. Among all the models developed, the 6-OHDA-lesioned rodents represent the models of choice to mimic PD motor symptoms and LID, thanks to their reproducibility and translational value. Under l-DOPA treatment, rodents sustaining 6-OHDA lesions develop abnormal involuntary movements with dystonic and hyperkinetic features, resembling what seen in dyskinetic PD patients. These models have been extensively validated by the evidence that dyskinetic behaviors are alleviated by compounds reducing dyskinesia in patients and non-human primate models of PD. This article will focus on the translational value of the 6-OHDA rodent models of LID, highlighting their main features, advantages and disadvantages in preclinical research.

Details

Authors
Organisations
External organisations
  • University of Cagliari
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences

Keywords

  • 6-OHDA, Dyskinesia, l-DOPA, Parkinson’s disease, Rodent model
Original languageEnglish
Pages (from-to)1137-1144
JournalJournal of Neural Transmission
Volume125
Issue number8
Early online date2017 Dec 14
Publication statusPublished - 2018
Publication categoryResearch
Peer-reviewedYes