Generating Excitotoxic Lesion Models of Huntington’s Disease

  • Mariah J. LelosEmail author
  • Stephen B. Dunnett
Part of the Methods in Molecular Biology book series (MIMB, volume 1780)


In Huntington’s disease (HD), the medium spiny projection neurons of the neostriatum degenerate early in the course of the disease. While genetic mutant models of HD provide an excellent resource for studying the molecular and cellular effects of the inherited polyQ huntingtin mutation, they do not typically present with overt atrophy of the basal ganglia, despite this being a major pathophysiological hallmark of the disease. By contrast, excitotoxic lesion models, which use quinolinic acid to specifically target the striatal projection neurons, are employed to study the functional consequences of striatal atrophy and to investigate potential therapeutic interventions that target the neuronal degeneration. This chapter provides a detailed guide to the generation of excitotoxic lesion models of HD in rats.


Excitotoxic lesion Huntington’s disease Quinolinic acid Motor Cognition Striatum Neurotoxin 



Our own work in this area has been supported by funding from the Medical Research Council, the EU FP7 Repair HD and NeuroStemCell Repair consortia, and Parkinson’s UK charity. We thank David Harrison for generating photographic material for the figure.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Brain Repair Group, School of BiosciencesCardiff UniversityWalesUK
  2. 2.Brain Repair GroupCardiff UniversityCardiffUK

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