Behavioral characterization of a unilateral 6-OHDA-lesion model of Parkinson's disease in mice

Behav Brain Res. 2005 Jul 1;162(1):1-10. doi: 10.1016/j.bbr.2005.02.023.


Parkinson's disease (PD) is one of the most common neurodegenerative disorders. Several toxin-induced animals models simulate the motor deficits occurring in PD. Among them, the unilateral 6-hydroxydopamine (6-OHDA) model is frequently used in rats and has the advantage of presenting side-biased motor impairments. However, the behavioral consequences of a unilateral 6-OHDA-lesion have, so far, not been described in detail in mice. The aim of this study was to characterize mice with unilateral 6-OHDA-lesions placed in the median forebrain bundle using several motor behavioral tests in order to identify the most suitable predictor of nigral cell loss. Mice underwent various drug-induced (amphetamine- and apomorphine-induced rotation) and spontaneous motor tests (cylinder, rotarod, elevated body swing, and stride length test). The amphetamine-induced rotation test, the cylinder and the rotarod test were most sensitive and reliable in detecting loss of tyrosine hydroxylase-immunoreactive cells in the substantia nigra. This study demonstrates that substantial and stable unilateral 6-OHDA-induced lesions can be established in mice, and that these lesions can be functionally assessed using several different side-bias-based behavioral tests. This mouse model offers the opportunity to use transgenic mouse strains and study the interactions between genes of interest and toxins in relation to Parkinson's disease etiology in the future.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic Agents
  • Amphetamine / pharmacology
  • Analysis of Variance
  • Animals
  • Antiparkinson Agents / pharmacology
  • Apomorphine / pharmacology
  • Behavior, Animal / drug effects*
  • Behavior, Animal / physiology
  • Cell Count / methods
  • Disease Models, Animal
  • Drug Interactions
  • Exploratory Behavior / drug effects
  • Female
  • Functional Laterality / drug effects
  • Functional Laterality / physiology*
  • Immunohistochemistry / methods
  • Linear Models
  • Medial Forebrain Bundle / injuries
  • Medial Forebrain Bundle / physiopathology
  • Mice
  • Mice, Inbred CBA
  • Motor Activity / drug effects
  • Neurons / drug effects
  • Neurons / metabolism
  • Oxidopamine*
  • Parkinson Disease / etiology
  • Parkinson Disease / physiopathology*
  • Predictive Value of Tests
  • Psychomotor Performance / drug effects
  • Rotarod Performance Test / methods
  • Rotation
  • Substantia Nigra / cytology
  • Substantia Nigra / metabolism
  • Time Factors
  • Tyrosine 3-Monooxygenase / metabolism
  • Ventral Tegmental Area / cytology
  • Ventral Tegmental Area / metabolism


  • Adrenergic Agents
  • Antiparkinson Agents
  • Oxidopamine
  • Amphetamine
  • Tyrosine 3-Monooxygenase
  • Apomorphine