Chapter 10 - Control of Motor Function by Adenosine A2A Receptors in Parkinson’s and Huntington’s Disease

Abstract

Adenosine A2A receptors are mainly expressed in the basal ganglia (BG) circuitry, which is responsible for the integration of sensorimotor information that controls the planning and initiation of voluntary movement. Specifically, adenosine A2A receptors are coexpressed with dopamine D2 receptors in the striatopallidal neurons of the BG, and this colocalization provides the anatomical basis for the existence of a functional antagonistic interaction between these receptors. Adenosine A2A receptors are involved in the pathogenesis of Parkinson’s disease (PD) and Huntington’s disease (HD), two neurological BG-related disorders with different peculiar motor and nonmotor symptoms. This chapter illustrates the role of A2A receptors as possible nondopaminergic strategies for the treatment of PD and HD. By discussing recent studies in rodents and nonhuman primates the chapter summarizes the pharmacology of adenosine A2A receptor antagonist and their interaction with dopaminergic, glutamatergic, cannabinoid and serotonin receptors, with specific relevance to cardinal motor symptoms of PD, motor fluctuations and dyskinesia induced by l-dopa therapy. In addition, the chapter describes the effects of A2A agonists and antagonists in rodent models of HD.