Adenosine A2A receptor blockade before striatal excitotoxic lesions prevents long term behavioural disturbances in the quinolinic rat model of Huntington's disease

Behav Brain Res. 2007 Jan 25;176(2):216-21. doi: 10.1016/j.bbr.2006.10.004. Epub 2006 Nov 22.

Abstract

Huntington's disease (HD) is a progressive neurodegenerative disorder, characterised by severe degeneration of basal ganglia, motor abnormalities, impaired cognitive function and emotional disturbances. Many of the distinct neuropathological features of HD are reproduced in rats by intrastriatal injections of the excitotoxin quinolinic acid (QA), and QA-induced excitotoxicity is partially prevented by administration of the A(2A) receptor antagonist prior to the QA injection. In this study, we assessed the neuroprotective effects of the adenosine A(2A) receptor antagonist SCH 58261 on the progressive behavioural alterations reported in the QA rat model of Huntington's disease. Male rats received i.p. SCH 58261 (0.01mg/kg) or vehicle 20min before a bilateral injection of quinolinic acid (QA, 300nmol/1mul) or its vehicle in the dorsal striatum. Motor activity and anxiety levels were analyzed in an open-field arena and in an elevated plus-maze at 2 weeks, 2 months and 6 months post-lesion. In QA-lesioned rats SCH 58261 prevented alterations of wall rearing behaviour starting from 2 weeks post-lesion while emotional changes (reduced anxiety) were back to control levels by 6 months post-lesion. These findings extend to the behavioural parameters the protective effects of SCH 58261 in the QA model of Huntington's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine A2 Receptor Antagonists
  • Analysis of Variance
  • Animals
  • Behavior, Animal
  • Behavioral Symptoms / etiology*
  • Behavioral Symptoms / prevention & control*
  • Corpus Striatum / drug effects*
  • Disease Models, Animal
  • Drug Interactions
  • Exploratory Behavior / drug effects
  • Huntington Disease / chemically induced
  • Huntington Disease / complications*
  • Huntington Disease / pathology*
  • Male
  • Maze Learning / drug effects
  • Neuroprotective Agents / administration & dosage
  • Pyrimidines / administration & dosage
  • Quinolinic Acid
  • Rats
  • Rats, Wistar
  • Receptor, Adenosine A2A / physiology*
  • Time Factors
  • Triazoles / administration & dosage

Substances

  • 5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine
  • Adenosine A2 Receptor Antagonists
  • Neuroprotective Agents
  • Pyrimidines
  • Receptor, Adenosine A2A
  • Triazoles
  • Quinolinic Acid