Premium
The Role of Angiotensin Receptor Type 1 on Corticotropin Releasing F actor Expressing Neurons in Auditory Fear Conditioning
Author(s) -
Hurt Robert,
Keifer Orion,
Ressler Kerry,
Marvar Paul
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.840.5
Subject(s) - fear conditioning , neuroscience , conditioning , psychology , receptor , medicine , amygdala , mathematics , statistics
Recent studies have suggested a potential role for the angiotensin receptor type 1 (AT 1 ) receptor in post‐traumatic stress disorder (PTSD) in both animals and humans. The current study attempts to better understand the underlying neuronal substrates that mediate angiotensin II in the extinction of conditioned fear. Mice with a conditional knockout of the AT 1 1R gene in corticotropin releasing factor (CRF) expressing neurons were used. CRF dysregulation is implicated in mood and anxiety disorders such as PTSD and therefore may impact AT 1 1R signaling. Our results demonstrate that deletion of the AT 1 R within CRF containing neurons decreases fear expression and enhances extinction compared to wild‐type controls. Administration of the selective AT 1 R antagonist losartan decreases fear expression in wild type mice, but has no effect on AT 1 R CRF neuron knockout mice. Baseline anxiety and locomotion levels were similar in both groups (1.2 m ± 0.19 vs 1.1 m ± 0.10) as well as baseline mean arterial pressure (MAP) (102 mmHg vs 107 mmHg). These results suggest that the action of angiotensin II at the AT 1 receptor on CRF producing neurons is a key component of cued fear consolidation or expression, and that drugs targeting the AT 1 receptor may be effective at reducing PSTD symptomology or may serve as adjuncts to exposure therapy for PTSD.