ABSTRACT
Phosphodiesterase-4 (PDE4) is a low Km, cyclic AMP-selective phosphodiesterase that is highly expressed in the central nervous system, including regions involved in the regulation of affective behavior, mood, and cognition. PDE4 also is involved in N-methyl d-aspartate receptor–mediated cyclic AMP signaling, which has been implicated in memory mechanisms and also may be involved in cognitive aspects of depression. Rolipram and other PDE4 inhibitors have been shown to be active in a number of preclinical assays sensitive to antidepressant drugs. PDE4 inhibitors also are active in a number of other models of antidepressant sensitivity. The function of PDE4 in memory processes began to be recognized at the beginning of the 1980s. PDE4 is involved in the mediation of long-term potentiation, a cellular model of synaptic plasticity and memory. The results of numerous studies carried out strong support that PDE4 inhibitors have antidepressant and memory-enhancing effects.
