Immediate‐early gene response to methamphetamine, haloperidol, and quinolinic acid is not impaired in Huntington's disease transgenic mice Journal Articles uri icon

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  • AbstractStriatal neurons in symptomatic Huntington's disease (HD) transgenic mice are resistant to a variety of toxic insults, including quinolinic acid (QA), kainic acid and 3‐nitropropionic acid. The basis for this resistance is currently unknown. To investigate the possibility that the immediate‐early gene (IEG) response is defective in symptomatic HD mice leading to a lack of response to these compounds, we examined the expression of c‐Fos and Krox 24 after administration of the indirect dopamine agonist methamphetamine, the dopamine D2 receptor antagonist haloperidol and the neurotoxin QA in 5‐ and 10‐week‐old R6/2 transgenic HD and wild‐type mice. Unlike wild‐type and pre‐symptomatic R6/2 transgenic HD mice, 10‐week‐old symptomatic HD mice were resistant to methamphetamine‐induced gliosis and QA lesion. There was, however, no difference in the number or distribution of c‐Fos‐immunoreactive nuclei 2 hr after single injections of methamphetamine or haloperidol among 5‐ and 10‐week‐old wild‐type mice and 5‐ and 10‐week‐old R6/2 HD mice. Similarly, despite their resistance to QA‐induced lesioning and lower basal levels of krox‐24 mRNA, the symptomatic R6/2 mice had equivalent increases in the amount of c‐fos and krox‐24 mRNA compared to wild‐type and pre‐symptomatic R6/2 HD mice as determined by in situ hybridization and densitometry 2 hr after QA administration. These data demonstrate that the c‐Fos and Krox 24 IEG response to dopamine agonists, dopamine antagonists and neurotoxic insult is functional in symptomatic R6/2 HD mice. Resistance to toxic insult in R6/2 mice may be conferred by interactions of mutant huntingtin with proteins or transcriptional processes further along the toxic cascade. © 2002 Wiley‐Liss, Inc.


  • MacGibbon, GA
  • Hamilton, LC
  • Crocker, SF
  • Costain, WJ
  • Murphy, Kathryn Mary
  • Robertson, HA
  • Denovan‐Wright, EM

publication date

  • February 2002

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