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Updated: Jun 11, 2026

The 6-hydroxydopamine Rat Model of Parkinson's Disease
Published on: October 27, 2021
A substance P mediated pathway contributes to 6-hydroxydopamine induced cell death
Emma Thornton1, Tuyet T B Tran, Robert Vink
1Discipline of Anatomy and Pathology, University of Adelaide, Adelaide, South Australia, Australia. Emma.Thornton@adelaide.edu.au
Abstract:
The neurotoxin 6-hydroxydopamine (6-OHDA) is used to induce dopaminergic cell death, resulting in insufficient striatal dopamine content in the basal ganglia and motor dysfunction typical of Parkinson's disease. Dopamine induces release of the neuropeptide substance P (SP) within the substantia nigra, whereas SP is able to potentiate striatal dopamine release, thus creating a positive feedback mechanism. Previous studies, however, have shown that elevated SP is detrimental to neuronal survival and motor function in acute brain injury. In the current study, we demonstrate that 6-OHDA increases SP production in meso-striatal organotypic co-culture. Moreover, there was a significant correlation between SP content and lactate dehydrogenase release, a marker of cell death, suggesting elevated SP production may contribute to 6-OHDA induced cell death in vitro.
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