Is there a major role for adenosine A2A receptors in anxiety?

Clinical investigations, pharmacological studies and models of genetically modified rodents have implicated adenosine in the etiology and modulation of different types of anxiety. Caffeine, a non-selective adenosine antagonist, has been involved in many of them. Adenosine seems to interact with other neurotransmitter systems and with some substances like alcohol, which elevate the basal levels of adenosine. A growing body of data describes the role of adenosine A1 and A2A receptors on anxiety. However, a differential role of adenosine receptors is not very clear. A1 receptor antagonists seem to be anxiogenic, but the absence of any effect of some of them and the opposite effects of others does not strongly support this conclusion. Human studies suggest that there is a susceptibility locus for panic disorder and agoraphobia within the receptor A2A gene. On the other hand, pharmacological data do not advocate for a clear implication of the A2A receptor. More research in this area is needed.