Caffeine as an antidote to depression caused by stress.

Kaster et al. do work that suggests adenosine A2A receptor (A2AR) antagonists might be therapeutic agents for relieving stress induced depression.:

Epidemiological studies show that individuals exposed to repeated stress, a major trigger of depression, increase their caffeine intake, which correlates inversely with the incidence of depression. However, the mechanism underlying this protective effect is unknown. We used an animal model of chronic unpredictable stress (CUS) to show that caffeine prevents the maladaptive changes caused by CUS in a manner mimicked by the selective blockade of adenosine A2A receptors (A2AR). CUS enhanced A2AR in synapses, and the selective elimination of neuronal A2AR abrogated CUS modifications. Moreover, A2AR blockade also afforded a therapeutic benefit, paving the way to consider A2AR blockers as a strategy to manage the negative impact of chronic stress on mood and memory.