Adenosine A2A receptor agonists produce a hypokinetic state (
catalepsy) that is believed to reflect antagonistic interaction of A2A and
dopamine D2 receptors in the basal ganglia. In addition to
catalepsy, pharmacological blockade of D2 receptors produces rigidity. However there are conflicting data about the effect of A2A agonists on muscle tone, with some reports indicating an increase, while other data suggest that A2A
catalepsy is dominated by
muscle hypotonia. We investigated the effect on resistance to imposed movements of systemic cataleptic doses of the selective A2A agonist
CGS21680 (5 mg/kg), and compared it with the effect of the D2 antagonist
raclopride (5 mg/kg), in rats. Total resistance is made up of elastic and viscous components. The elastic component is velocity independent, and is referred to as "stiffness," whereas viscosity, which dampens responses to imposed movements, is velocity dependent. Using a method for quantifying total joint resistance that enabled separate identification of stiffness and viscosity, we found that during
catalepsy evoked by either
drug there was a clear increase in joint rigidity. Both
CGS21680 and
raclopride significantly increased joint stiffness, the velocity independent component of rigidity that is most affected in
Parkinsonism. In contrast, the effect of
CGS21680 on the velocity-dependent viscosity component was less robust than for
raclopride, and did not reach significance, possibly reflecting an interaction with
sedative effects via extrastriatal receptors. The effect of
CGS21680 and
raclopride on joint stiffness is thus consistent with previous findings suggesting functional antagonism of A2A and D2 receptors in the basal ganglia.