Adenosine A(2A) antagonism increases striatal glutamate outflow in the quinolinic acid rat model of Huntington's disease.
In the quinolinic acid (QA)-rat model of Huntington's disease (HD), 15 days after QA injection, striatal glutamate, measured by in vivo microdialysis, was unchanged while a significant decrease in adenosine occurred. The decrease in adenosine may depend on QA-induced striatal cell loss. Probe perfusion of the adenosine A(2A) receptor antagonist SCH 58261 significantly increased striatal glutamate outflow, suggesting a potential detrimental effect of A(2A) antagonism at later stages of the neurodegenerative process induced by QA.
Gianfriddo
Marco
M
Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy.
Corsi
Claudia
C
Melani
Alessia
A
Pèzzola
Antonella
A
Reggio
Rosaria
R
Popoli
Patrizia
P
Pedata
Felicita
F
D000241:Adenosine / Q000032:analysis; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D005110:Extracellular Space / Q000737:chemistry; D018698:Glutamic Acid / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D006816:Huntington Disease / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D017551:Microdialysis; D023421:Models, Animal; D018696:Neuroprotective Agents / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines / Q000494:pharmacology; D017378:Quinolinic Acid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology
C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D018696:Neuroprotective Agents; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D014230:Triazoles; D018698:Glutamic Acid; D017378:Quinolinic Acid; D000241:Adenosine