A2A/D2 receptor heteromerization in a model of Parkinson's disease. Focus on striatal aminoacidergic signaling

The present manuscript mainly summarizes the basic concepts and the molecular mechanisms underlying adenosine A2A-dopamine D2 receptor–receptor interactions in the basal ganglia. Special emphasis is placed on neurochemical, behavioral and electrophysiological findings supporting the functional role that A2A/D2 heteromeric receptor complexes located on striato-pallidal GABA neurons and corticostriatal glutamate terminals play in the regulation of the so called “basal ganglia indirect pathway”. Furthermore, the role of A2A/mGluR5 synergistic interactions in striatal neuron function and dysfunction is discussed. The functional consequences of the interactions between striatal adenosine A2A, mGluR5 and dopamine D2 receptors on striatopallidal GABA release and motor behavior dysfunctions suggest the possibility of simultaneously targeting these receptors in Parkinson's disease treatment. This article is part of a Special Issue entitled Brain Integration.This article is part of a Special Issue entitled: Brain Integration.