Phosphodiesterase 4 (PDE4) is an important regulator of cyclic adenosine monophosphate (cAMP) levels in the body and brain. Specific inhibitors of this PDE subtype, such as rolipram, are reported to have antidepressant effects via increasing cAMP signaling. In the present study, we investigated depressive-like behavior in rats after region-specific upregulation of cAMP signaling by intra-hippocampal and intra-accumbal infusions of rolipram. Our results demonstrate a dissociative role for cAMP signaling in the nucleus accumbens and hippocampus in depressive-like behavior. That is, rats showed an increase in anhedonic behavior when rolipram was administered in the nucleus accumbens, while hippocampal administration reduced anhedonia. This is in line with previous reports which described an analogous dissociative effect after altering hippocampal and accumbal expression of the transcription factor cAMP responsive element binding protein (CREB). Although CREB is generally regarded as an important downstream target of cAMP, in the present study CREB phosphorylation was unaffected by the repeated rolipram infusions. Thus, the exact underlying mechanism of the regionspecific pro- and antidepressant effects of rolipram remains to be elucidated.
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