The 6-OHDA (6-hydroxydopamine) rat model is a classic toxin-based model of Parkinson's disease that produces selective destruction of catecholaminergic neurons[1]. Unlike the MPTP model, 6-OHDA is administered directly into the brain, producing precise, unilateral lesions that allow each animal to serve as its own control.
6-OHDA was first used to model PD in the 1960s by Ungerstedt, who demonstrated that bilateral injections produced a hypokinetic syndrome resembling parkinsonism. The unilateral model was later developed to allow for detailed behavioral and pharmacological studies[2].
| Injection Site | Effect | Common Use |
|---|---|---|
| Medial forebrain bundle | >95% DA depletion | Rotation behavior |
| Substantia nigra | Partial SNc lesion | Selective degeneration |
| Striatum | Retrograde degeneration | Progressive model |
| Advantage | Description |
|---|---|
| Precise lesion control | Direct brain injection |
| Self-control design | Unilateral model allows within-animal comparison |
| Behavioral readouts | Multiple validated behavioral tests |
| Drug screening | Rotation test for anti-parkinsonian drugs |
| Anatomical precision | Well-defined injection targets |
| Limitation | Description |
|---|---|
| Surgical procedure | Requires stereotaxic surgery |
| No Lewy bodies | Lacks protein inclusions |
| Acute lesion | Rapid degeneration, not chronic |
| Non-physiological | Direct toxin injection is not natural |
The unilateral model allows quantification of:
Used to test:
Investigation of:
Ungerstedt U. 6-Hydroxydopamine-induced degeneration of central monoamine neurons. Eur J Pharmacol. 1968. ↩︎
Dekundy A, et al. 6-Hydroxydopamine lesions in rat brain. Nat Protoc. 2007. ↩︎