Abstract: Objective To explore the role of phosphodiesterase-2 activity in the amygdala produces anxiolytic-like effects in mice. Methods: Male ICR mice were implanted with guide cannula targeting the central nucleus of the amygdala bilaterally.  Following recovery from surgery, mice were administered either Bay 60-7550 or lentiviral vector/microRNA targeted to PDE2. The effects of pharmacological inhibition were assessed 30 min post-treatment while those of PDE2 knockdown were assessed beginning one week after treatment with the lentiviral vector/microRNA. Behavioral effects were assessed in the elevated plus-maze and the tail-suspension tests; ODQ was used to assess cyclic GMP involvement. Cannula placement and viral vector localization were determined histologically via its GFP tag. Results: Administration of Bay 60-7550 into the central nucleus of the amygdala resulted in anxiolytic- and antidepressant-like effects on behavior of mice in the elevated plus-maze and tail-suspension test, respectively; these effects were blocked by pretreatment with ODQ. Viral vector/microRNA-induced knockdown of PDE2 resulted in similar effects on behavior in these tests, which also were blocked by ODQ. The treatment reduced PDE2 expression by approximately 80%. Conclusion:The present study does provide an additional line of support that reduced PDE2 activity, achieved in this case via lentiviral vector/microRNA-induced knockdown, is associated with such behavioral effects，resulting from treatment with NO donors, which also increase cyclic GMP signaling.

Key words: phosphodiesterase-2, anxiety, Bay 60-7550, amygdala, microRNA, mice