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Adenosine Receptor-DR Heteromers A2A-D2R Heteromers The C-terminal tail of the A2AR and the intracellular loop3 of the D2R form antagonistic heteromers through direct electrostatic interactions in striatopallidal GABAergic neurons and glial cells (52), resulting in a rapid switch from D2R-Gi coupling toward -arrestin2/Akt/GSK-3 signaling (53, 54), and reducing the activity of the striatopallidal GABA/enkephalin-mediated inhibition of the excitatory glutamate thalamocortical pathway through Ca2+ and cAMP/PKA pathway whose activation involves the phosphorylation of different PKA substrates, including DARPP-32, CREB, and -amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) (55, 56)

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