Catalepsy induced by a blockade of dopamine D1 or D2 receptors was reversed by a concomitant blockade of adenosine A2A receptors in the caudate-putamen of rats

The present study sought to determine, in more detail, the effects of an unselective and a selective adenosine A(2A) receptor blockade on catalepsy induced by a blockade of dopamine D-1 or D-2 receptors in rats. The results demonstrated that systemic administration of the unselective A(1)/A(2) receptor antagonist, theophylline and the selective A(2A) receptor antagonist, CSC potently reversed catalepsy induced by a systemic D-2 receptor blockade with raclopride or by a bilateral blockade of D-2 receptors in the caudate-putamen (CPu) with S(-)sulpiride. Likewise, systemic administration of theophylline and CSC reversed catalepsy induced by a systemic D-1 receptor blockade with SCH23390; theophylline also counteracted catalepsy after an intra-CPu D-1 receptor blockade with SCH23390. Intracerebral co-microinfusions of the selective A(2A) receptor antagonist, MSX-3 together with a D-1 (SCH23390) or D-2 receptor [S(-) sulpiride] antagonist revealed that catalepsy due to intra-CPu D-1 or D-2 receptor blockade can be potently reversed by an intra-CPu A(2A) receptor blockade. In conclusion, our results with systemic and intra-CPu drug administration demonstrate that D-1 and D-2 receptor-mediated catalepsy can both be reversed by a concomitant blockade of A(2A) receptors. Our results implicate that the CPu is a critical neural substrate for antagonistic interactions of a D-1/D-2 receptor blockade and an A(2A) receptor blockade in control of motor activity. The present results provide further support for the view that A(2A) receptor antagonists may be potential therapeutics for the treatment of Parkinson's disease.