Research Article

6-OHDA Model of Parkinson’s Disease

 

Key features, outcomes, behavior tests and the validity of the 6OHDA

The 6-hydroxydopamine (6-OHDA) model of Parkinson’s Disease (PD) was the first model of PD generated, and has since been widely used to investigate parkinsonism in rodents. The model was originally developed following the discovery that injecting 6-OHDA into the substantia nigra pars compacta (SNpc) caused anterograde degen- eration of the nigrostriatal dopaminergic system, producing a loss of dopaminergic neurons in the SNpc and loss of dopaminergic terminals in the striatum (to which the SNpc projects), similar to that observed in Parkinson’s disease. 6-OHDA is similar in structure to dopamine, but the presence of an additional hydroxyl group makes it toxic to dopaminergic neurons. Once in the cytosol, 6-OHDA auto-oxidizes to form reactive oxygen species, which are thought to cause neurodegeneration by reducing levels of anti-oxidant enzymes, elevating iron, and inhibiting mitochondrial respiration.

 

The main features of this model that have made it popular are that it is relatively fast, inexpensive and simple to implement, and that the lesions it produces are reproducible and substantial.

 

This article discusses:

  • Contributions of the model to our understanding and treating of PD
  • Assessing the validity of the model
  • Key features, the benefits and drawbacks
  • Three dosing sites and outcomes that are expected
  • Behavior tests and what they tell us
  • Tests of non-motor function