Moreover, some studies have found that caffeine reverts memory impairment in a depression-prone mouse strain with upregulation of adenosine A2A receptors in the hippocampus (Machado et al., 2017), while selective A2AR knockout in the forebrain region (striatum, hippocampus, and cortex) induces anxiety-like behavior (Wei et al., 2014). Here, ADORA2A is linked to depressive disorder.