MOTOR EFFECTS INDUCED BY A BLOCKADE OF ADENOSINE A(2A) RECEPTORS IN THE CAUDATE-PUTAMEN

MOTOR effects mediated through adenosine A(2A) receptors within the ca udate-putamen were investigated in rats using bilateral microinfusions of MSX-3 (9 mu g in 1 mu l per side), a water-soluble phosphate prodr ug oi the selective A(2A) receptor antagonist MSX-2. Blockade of stria tal A(2A) receptors produced a significant motor stimulation measured by an enhanced sniffing activity. Furthermore, catalepsy induced by sy stemic dopamine D-1 (0.75 mg/kg SCH23390, i.p.) or dopamine D-2 recept or blockade (1.5 mg/kg raclopride, i.p.) was potently reversed. These findings suggest that A(2A) receptor within the caudate-putamen are to nically activated by endogenous adenosine and that a striatal A(2A) re ceptor blockade produces motor stimulant effects, in particular in ani mals 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.