These data suggest that long-form PDE4Ds, at least PDE4D4 and PDE4D5, may be the promising targets for the development of PDE4 variant-selective inhibitors as the new pharmacotherapies for depressive disorders and neurodegenerative diseases involving memory deficits.
The rat model confirms Pde4d's role in depression but not in spatial learning or memory enhancement and shows for the first time higher fear conditioning and altered extinction compared with controls.
These results suggest that PDE4D is an essential mediator of the antidepressant-like effects of rolipram, and that PDE4D-regulated cyclic adenosine monophosphate signaling may play a role in the pathophysiology and pharmacotherapy of depression.