Adenosine A_2A receptors blockade attenuates dexamethasone-induced alterations in cultured astrocytes

Anxiety involves abnormal glucocorticoid signalling and altered glia-neuron communication in brain regions processing emotional responses. Adenosine A_2A receptor (A_2AR) blockade ameliorates mood and memory impairments by preventing synaptic dysfunction and astrogliosis. Since the glucocorticoid dexamethasone (DEX) can mimic early life-stress conditions, leading to anxiety-like behaviours, we now tested if A_2AR blockade prevents alterations in the morphology and function of astrocytes exposed to DEX. Cultured astrocytes exposed to DEX exhibited an up-regulation of astrocytic markers (GFAP, connexin-43 and glutamine synthetase), as well as of A_2AR. Moreover, DEX enhanced ATP and glutamate release and increased basal astrocytic Ca²⁺ levels. The selective A_2AR antagonist SCH58261 prevented DEX-induced alterations in ATP release and basal Ca²⁺ levels but did not affect DEX-induced alteration of glutamate release and astrocytic markers. These findings suggest that alterations in astrocytes function, which might contribute to abnormal glucocorticoid brain signalling, are controlled by A_2AR, and therefore, reinforce the relevance of A_2AR as a potential therapeutic target to manage mood disorders.