Furthermore, future studies should investigate the possible contribution of this proposed feedback facilitatory loop to the synaptic dysfunction characteristic of different neuropsychiatric diseases, in view of the previously reported up-regulation of synaptic A2AR in numerous brain diseases (e.g. [11, 12, 18, 24, 68], as well as the established role of released ATP as a danger signal in the brain [71]. This evidence concerns the gene ADORA2A and brain disorder.