Motor effects induced by a blockade of adenosine A2A receptors in the caudate-putamen

MOTOR effects mediated through adenosine A(2A) receptors within the caudate-putamen were investigated in rats using bilateral microinfusions of MSX-3 (9 mu g in 1 mu l per side), a water-soluble phosphate prodrug of the selective A(2A) receptor antagonist MSX-2. Blockade of striatal A(2A) receptors produced a significant motor stimulation measured by an enhanced sniffing activity. Furthermore, catalepsy induced by systemic dopamine D-1 (0.75 mg/kg SCH23390, i.p.) or dopamine D-2 receptor blockade (1.5 mg/kg raclopride, i.p.) was potently reversed. These findings suggest that A(2A) receptor within the caudate-putamen are tonically activated by endogenous adenosine and that a striatal A(2A) receptor blockade produces motor stimulant effects, in particular in animals with dopamine hypofunction. The present results support the view that A(2A) receptor antagonists may be potentially useful therapeutics for the treatment of Parkinson's disease. (C) 1998 Rapid Science Ltd.