The effect of unpredictable chronic mild stress on depressive-like behavior and on hippocampal A1 and striatal A2A adenosine receptors

This study examined the effects of two chronic stress regimens upon depressive-like behavior, A1 and A2A adenosine receptor binding and immunocontent. Male rats were subjected to unpredictable chronic mild stress (UCMS) or to chronic restraint stress (CRS) for 40 days. Subsequently, depressive-like behaviors (forced swimming and consumption of sucrose) were evaluated, and A1 adenosine or A2A adenosine receptors were examined in the hippocampus or striatum, respectively. UCMS animals demonstrated depressive-related behaviors (decrease in sucrose consumption and increased immobility in the forced swimming test). This group also presented increased A1 adenosine receptor binding and immunoreactivity in hippocampus, as well as increased striatal A2A adenosine receptor binding in the striatum, without alteration in immunoreactivity. Conversely, the chronic restraint stress group displayed only an increase in A1 adenosine receptor binding and no alteration in the other parameters evaluated. We suggest that the alteration in adenosine receptors, particularly the upregulation of striatal A2A adenosine receptors following UCMS, could be associated with depressive-related behavior.

► UCMS rats demonstrated depressive-related behaviors.
► UCMS and CRS rats presented increased A1R in the hippocampus.
► UCMS rats presented increased A2AR in the striatum.
► Upregulation of A2AR following UCMS may be associated with depressive behavior.