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 amygd...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.展开更多
文摘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.
