Motor effects induced by a blockade of adenosine A2A receptors in the caudate-putamen.
Motor effects mediated through adenosine A2A receptors within the caudate-putamen were investigated in rats using bilateral microinfusions of MSX-3 (9 microg in 1 microl per side), a water-soluble phosphate prodrug of the selective A2A receptor antagonist MSX-2. Blockade of striatal A2A receptors produced a significant motor stimulation measured by an enhanced sniffing activity. Furthermore, catalepsy induced by systemic dopamine D1 (0.75 mg/kg SCH23390, i.p.) or dopamine D2 receptor blockade (1.5 mg/kg raclopride, i.p.) was potently reversed. These findings suggest that A2A receptors within the caudate-putamen are tonically activated by endogenous adenosine and that a striatal A2A receptor blockade produces motor stimulant effects, in particular in animals with dopamine hypofunction. The present results support the view that A2A receptor antagonists may be potentially useful therapeutics for the treatment of Parkinson's disease.
Hauber
W
W
Department of Animal Physiology, Institute of Biology, University of Stuttgart, Germany.
Nagel
J
J
Sauer
R
R
Müller
C E
CE
D000818:Animals; D001552:Benzazepines / Q000633:toxicity; D002375:Catalepsy / Q000139:chemically induced; D002421:Caudate Nucleus / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000633:toxicity; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D011355:Prodrugs / Q000494:pharmacology*; D058915:Purinergic P1 Receptor Antagonists; D011699:Putamen / Q000187:drug effects*; D020891:Raclopride; D051381:Rats; D017207:Rats, Sprague-Dawley; D012457:Salicylamides / Q000633:toxicity; D014970:Xanthines / Q000494:pharmacology*
C113601:3-(3-hydroxypropyl)-8-(3-methoxystyryl)-7-methyl-1-propargylxanthine; D001552:Benzazepines; D018492:Dopamine Antagonists; C113602:MSX 3 compound; D011355:Prodrugs; D058915:Purinergic P1 Receptor Antagonists; D012457:Salicylamides; D014970:Xanthines; D020891:Raclopride