Dopamine/Adenosine Interactions Related to Tremor in Animal Models of Parkinsonism

Abstract

Adenosine A2A receptor antagonists have been shown to exert antiparkinsonian effects in human clinical studies and animal models. The present chapter reviews experiments that were conducted to study the role of adenosine A2A receptors in the regulation of tremor. In particular, these studies have focused on the tremulous jaw movement model of Parkinsonian tremor. Systemic and intrastriatal injections of adenosine A2A receptor antagonists have been shown to reduce the oral tremor induced by dopamine antagonists, dopamine depletion, and cholinomimetic stimulation. Adenosine A2A receptor knockout mice are resistant to the pharmacological induction of tremulous jaw movements. Moreover, stimulation of adenosine A2A receptors with CGS 21680 was capable of inducing tremulous jaw movements. These results demonstrate that adenosine A2A antagonists can exert anti-tremor effects in animal models, which supports their use as antiparkinsonian agents in humans.