Increased Protein Kinase A Activity in the Prkar1a-defective Mouse is Associated with Hyperarousal and Increased Anxiety
Abstract
The role of the cAMP/PKA signaling in the molecular pathways involved in fearand memory is well established. We recently reported that a Prkar1a heterozygote (Prkar1a(+/-)) mouse that was developed in our lab showed tissue-specific increased PKA activity that wasassociated with anxiety-like behavioral phenotype. This proposal tested the following hypothesis: mice with the loss of one Prkar1a allele will display an anxiety-like phenotype and subsequent increased vulnerability to stress associated with increased PKA activity in brain areas involved with processing of emotional stimuli and anxiety. We measured behavioral response to stress, neural activation, and PKA activity in brain areas after exposure to predator odor or vehicle in male Prkar1a(+/-) and WT littermates. Significant differences were found between Prkar1a(+/-) and WT mice in the behavioral response to stress. The behavioral response of Prkar1a(+/-) mice was consistent with the prediction error model of anxiety. In addition, basal and total PKA activities were independently associated with genotype and stress, and an interaction between genotype and stress was shown. Results of cFos expression in Prkar1(a+/-) mice showed treatment effect in basolateral amygdala only. These results suggest that the alterations in PKA signaling in Prkar1(a+/-) mice are not ubiquitous in the brain; tissue-specific effects of the cAMP/PKA pathway are related to the stress response and anxiety-like behavior.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 09, 2011
- Accession Number
- AD1013349
Entities
People
- Margaret F. Keil
Organizations
- Uniformed Services University of the Health Sciences