The possible antidepressant mechanism of adenosine is related to energy metabolism, levels of brain-derived neurotrophic factor and GABA, which were both mediated by adenosine receptors A1R and A2AR. In particular, the activation of A2AR could promote the accumulation of BDNF and GABA, thereby alleviating depression [63]. Here, ADORA2A is linked to major depressive disorder.