Adenosine A2A receptor blockade before striatal excitotoxic lesions prevents long term behavioural disturbances in the quinolinic rat model of Huntington's disease.
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.
Scattoni
Maria Luisa
ML
Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena 299, I-00161 Rome, Italy.
Valanzano
Angelina
A
Pezzola
Antonella
A
March
Zena De
ZD
Fusco
Francesca Romana
FR
Popoli
Patrizia
P
Calamandrei
Gemma
G
D058917:Adenosine A2 Receptor Antagonists; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001526:Behavioral Symptoms / Q000209:etiology* / Q000517:prevention & control*; D003342:Corpus Striatum / Q000187:drug effects*; D004195:Disease Models, Animal; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects; D006816:Huntington Disease / Q000139:chemically induced / Q000150:complications* / Q000473:pathology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage; D017378:Quinolinic Acid; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A / Q000502:physiology*; D013997:Time Factors; D014230:Triazoles / Q000008:administration & dosage
C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058917:Adenosine A2 Receptor Antagonists; D018696:Neuroprotective Agents; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D014230:Triazoles; D017378:Quinolinic Acid