A2AR are enriched in the striatum with a predominant post-synaptic localization to control dopamine signaling60, with comparatively lower densities in brain regions associated with depression, such as mPFC, hippocampus, and amygdala61,62, where A2AR are mostly presynaptic controlling synaptic plasticity (reviewed in11) and synaptic remodeling63. This evidence concerns the gene ADORA2A and major depressive disorder.