Anxiogenic-Like Behavioral Phenotype of Mice Deficient in Phosphodiesterase 4B (PDE4B)

摘要: Phosphodiesterase-4 (PDE4), an enzyme that catalyzes the hydrolysis of cyclic AMP and plays a critical role in controlling its intracellular concentration, has been implicated depression- anxiety-like behaviors. However, functions four PDE4 subfamilies (PDE4A, PDE4B, PDE4C, PDE4D) remain largely unknown. In animal tests sensitive to anxiolytics, antidepressants, memory enhancers, or analgesics, we examined behavioral phenotype mice deficient PDE4B (PDE4B-/-). Immunoblot analysis revealed loss expression cerebral cortex amygdala PDE4B-/- mice. The reduction was accompanied by decreases activity brain regions Compared PDE4B+/+ littermates, displayed anxiogenic-like behavior, as evidenced decreased head-dips time spent head-dipping holeboard test, reduced transitions on light side light-dark transition initial exploration rears open-field test. Consistent with increased levels plasma corticosterone. addition, these also showed modest increase proliferation neuronal cells hippocampal dentate gyrus. forced-swim exhibited immobility; however, this not supported results from tail-suspension did display changes memory, locomotor activity, nociceptive responses. Taken together, suggest subfamily is involved signaling pathways contribute effects behavior.