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

Abstract

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 D₁ or D₂ receptors in rats. The results demonstrated that systemic administration of the unselective A₁/A₂ receptor antagonist, theophylline and the selective A_2A receptor antagonist, CSC potently reversed catalepsy induced by a systemic D₂ receptor blockade with raclopride or by a bilateral blockade of D₂ receptors in the caudate-putamen (CPu) with S(–)sulpiride. Likewise, systemic administration of theophylline and CSC reversed catalepsy induced by a systemic D₁ receptor blockade with SCH23390; theophylline also counteracted catalepsy after an intra-CPu D₁ receptor blockade with SCH23390. Intracerebral co-microinfusions of the selective A_2A receptor antagonist, MSX-3 together with a D₁ (SCH23390) or D₂ receptor [S(–) sulpiride] antagonist revealed that catalepsy due to intra-CPu D₁ or D₂ 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 D₁ and D₂ 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/D₂ 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.