This study examined the effects of two chronic stress regimens upon depressive-like behavior, A 1 and A 2A adenosine receptor binding and immunocontent. Male rats were subjected to unpredictable chronic mild stress (UCMS) or to chronic restraint stress (CRS) for 40days. Subsequently, depressive-like behaviors (forced swimming and consumption of sucrose) were evaluated, and A 1 adenosine or A 2A 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 A 1 adenosine receptor binding and immunoreactivity in hippocampus, as well as increased striatal A 2A adenosine receptor binding in the striatum, without alteration in immunoreactivity. Conversely, the chronic restraint stress group displayed only an increase in A 1 adenosine receptor binding and no alteration in the other parameters evaluated. We suggest that the alteration in adenosine receptors, particularly the upregulation of striatal A 2A adenosine receptors following UCMS, could be associated with depressive-related behavior.