Fig. 6.

Schematization of caffeine action on its adenosine receptors targets and their impact in NMDAR-mediated responses. At the post-synaptic level caffeine acts via A₁R blockade, affecting Ca²⁺ homeostasis by promoting an increase in Ca²⁺ entry through NMDAR. At the pre-synaptic level, caffeine, by blocking A_2AR, decreases glutamate release, which may counteract the excitatory action and, in such way, contribute to maintaining synaptic transmission homeostasis. Changes in the relative contribution to these two opposing actions throughout life as well as under different pathologies may lead to different global actions of caffeine on NMDAR-mediated responses