ADORA2A and schizophrenia: Since decreased glutamatergic neurotransmission and increased dopaminergic activity contribute to the pathophysiology of schizophrenia and related psychiatric disorders, the ability of A2AR to integrate dopaminergic and glutamatergic systems indicates that adenosine acting at A2AR may modulate both positive (by preventing hyper-dopaminergic activity) and negative (by preventing hypo-glutamatergic activity) symptoms of schizophrenia [42].