Reduced phosphodiesterase-2 activity in the amygdala results in anxiolytic-like effects on behavior in mice

Abstract

Background:

Phosphodiesterase-2 (PDE2) is a cyclic nucleotide phosphodiesterase and is highly expressed in the amygdala, which suggests its important role in anxiety-like behavior.

Aims:

The present study examined whether reduced PDE2A expression in the central nucleus of the amygdala (CeA) produces anxiolytic-like effects in mice.

Methods:

PDE2A knockdown in amygdaloid (AR5) cells or the CeA was established using a lentiviral vector-based siRNA system. The anxiety-like behaviors were detected by the elevated plus maze (EPM) and hole-board tests in mice. The related proteins involved in cAMP/cGMP-dependent signaling, such as specific marker VASP^ser239, CREB^ser133 and BDNF were detected by immunoblot analysis.

Results:

PDE2A inhibition in AR-5 cells resulted in increases in cAMP/cGMP-related pVASP^ser239 and pCREB^ser133. Behavioral tests showed that PDE2A knockdown in the CeA induced anxiolytic-like effects as evidenced by the increases in percentages of open-arm entries and time spent in the open arms in the EPM test, and the increases in head dips and time spent in head dipping in the hole-board test. However, these anxiolytic-like effects were antagonized by pre-treatment of soluble guanylyl cyclase inhibitor ODQ or adenylate cyclase inhibitor SQ. Furthermore, PDE2A knockdown significantly increased pVASP^Ser239, pCREB^Ser133 and decreased BDNF expression in the amygdala. Pre-intra-CeA of ODQ or SQ reversed or partially prevented the eﬀects of PDE2A knockdown on these proteins.

Conclusions:

The results suggest that PDE2A plays a crucial role in the regulation of anxiety by the cGMP/cAMP-dependent pVASP-pCREB-BDNF signaling pathway.

Keywords

PDE2 anxiety cGMP/cAMP pVASP pCREB central nucleus of the amygdala (CeA)

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