Adenosine receptors and Parkinson's disease. Relevance of antagonistic adenosine and dopamine receptor interactions in the striatum

Evidence for a role of dopaminergic neurotransmission in the motor effects of adenosine antagonists, such as caffeine, is reviewed, based on the existence of specific antagonistic interactions between specific subtypes of adenosine and dopamine receptors in the striatum. Both adenosine A1 and adenosine A2A receptor antagonists induce motor activation in rodents. At least a certain degree of dopaminergic activity is required to obtain adenosine antagonist-induced motor activation, with adenosine A1 antagonists being the most sensitive and non-selective adenosine antagonists the most resistant to striatal dopamine depletion. When considering long-term treatment with adenosine antagonists concomitant administration of dopamine agonists might be required in order to obtain strong motor effects (cross-sensitization) and to avoid the development of telerance.