4.6 Article

Studies of mice with cyclic AMP-dependent protein kinase (PKA) defects reveal the critical role of PKA's catalytic subunits in anxiety

Journal

BEHAVIOURAL BRAIN RESEARCH
Volume 307, Issue -, Pages 1-10

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbr.2016.03.001

Keywords

Anxiety; Amygdala; Protein kinase a; Knockout mice

Funding

  1. NICHD, NIH [Z01-HD008920-01]
  2. Uniformed Services University of the Health Sciences
  3. Office of Naval Research
  4. Department of Pediatrics, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece

Ask authors/readers for more resources

Cyclic adenosine mono-phosphate-dependent protein kinase (PICA) is critically involved in the regulation of behavioral responses. Previous studies showed that PKA's main regulatory subunit, R1 alpha, is involved in anxiety-like behaviors. The purpose of this study was to determine how the catalytic subunit, C alpha, might affect R1 alpha's function and determine its effects on anxiety-related behaviors. The marble bury (MB) and elevated plus maze (EPM) tests were used to assess anxiety-like behavior and the hotplate test to assess nociception in wild type (WT) mouse, a Prkar1a heterozygote (Prkar1a(+/-)) mouse with haploinsufficiency for the regulatory subunit (R1 alpha), a Prkaca heterozygote (Prkar1a(+/-)) mouse with haploinsufficiency for the catalytic subunit (C alpha), and a double heterozygote mouse (Prkar1a(+/-)/Prkaca(+/-)) with haploinsufficiency for both R1 alpha and C alpha. We then examined specific brain nuclei involved in anxiety. Results of MB test showed a genotype effect, with increased anxiety-like behavior in Prkar1a(+/-) and Prkar1a(+/-)/Prkaca(+/-) compared to WT mice. In the EPM, Prkar1a(+/-) spent significantly less time in the open arms, while Prkaca(+/-) and Prkar1a(+/-)/Prkaca(+/-) mice displayed less exploratory behavior compared to WT mice. The loss of one Prkar1a allele was associated with a significant increase in PKA activity in the basolateral (BLA) and central (CeA) amygdala and ventromedial hypothalamus (VMH) in both Prkar1a(+/-) and Prkar1a(+/-)/Prkaca(+/-) mice. Alterations of PICA activity induced by haploinsufficiency of its main regulatory or most important catalytic subunits result in anxiety-like behaviors. The BLA, CeA, and VMH are implicated in mediating these PICA effects in brain. Published by Elsevier B.V.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available