ADORA2A and Anxiety: After 3-weeks antagonism by caffeine, endogenous A2AR signaling was inhibited, optogenetic activation of optoA2AR captured the physiological function of the native A2AR. Light activation of dHPC adenosine A2A receptors reversed the behavioral alterations caused by caffeine, leading to impaired memory, while light activation of vHPC adenosine A2A receptors decreased caffeine-induced anxiety, further confirming the dissociation between the roles of the ventral and dorsal hippocampal A2A receptors in caffeine’s effects.