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Overactivity of astroglial A 2A R induces extrasynaptic and postsynaptic mGluR1 and mGluR5 coupling to Gq protein (G protein subunit, which activates phospholipase and thereby increases diacylglycerol and inositol-triphosphate levels) by enhancing astroglial glutamate release, which can further increase intracellular calcium levels and lead to inhibition of D 2 R signaling in A 2A R-D 2 R and A 2A R-mGluR5 complexes (Figure 1) [37]