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