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 2A R) 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 2A R 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 2A R. Moreover, DEX enhanced ATP and glutamate release and increased basal astrocytic Ca 2+ levels. The selective A 2A R antagonist SCH58261 prevented DEX-induced alterations in ATP release and basal Ca 2+ 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 2A R, and therefore, reinforce the relevance of A 2A R as a potential therapeutic target to manage mood disorders.