title: Angiotensin type 1a receptors on corticotropin-releasing factor neurons contribute to the expression of conditioned fear.
abstract: Although generally associated with cardiovascular regulation, angiotensin II receptor type 1a (AT1a R) blockade in mouse models and humans has also been associated with enhanced fear extinction and decreased post-traumatic stress disorder (PTSD) symptom severity, respectively. The mechanisms mediating these effects remain unknown, but may involve alterations in the activities of corticotropin-releasing factor (CRF)-expressing cells, which are known to be involved in fear regulation. To test the hypothesis that AT1a R signaling in CRFergic neurons is involved in conditioned fear expression, we generated and characterized a conditional knockout mouse strain with a deletion of the AT1a R gene from its CRF-releasing cells (CRF-AT1a R((-/-)) ). These mice exhibit normal baseline heart rate, blood pressure, anxiety and locomotion, and freeze at normal levels during acquisition of auditory fear conditioning. However, CRF-AT1a R((-/-)) mice exhibit less freezing than wild-type mice during tests of conditioned fear expression-an effect that may be caused by a decrease in the consolidation of fear memory. These results suggest that central AT1a R activity in CRF-expressing cells plays a role in the expression of conditioned fear, and identify CRFergic cells as a population on which AT1 R antagonists may act to modulate fear extinction.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine.|Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes National Primate Research Center, Atlanta, GA.
authors.forename: R C
authors.initials: RC
authors.lastname: Hurt
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine.|Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes National Primate Research Center, Atlanta, GA.
authors.forename: J C
authors.initials: JC
authors.lastname: Garrett
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine.|Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes National Primate Research Center, Atlanta, GA.
authors.forename: O P
authors.initials: OP
authors.lastname: Keifer
authors.affiliation: Farquhar College of Arts and Sciences.|Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL.
authors.forename: A
authors.initials: A
authors.lastname: Linares
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL.
authors.forename: L
authors.initials: L
authors.lastname: Couling
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL.|Department of Pharmacology and Physiology, College of Medicine, Georgetown University, Washington, DC.
authors.forename: R C
authors.initials: RC
authors.lastname: Speth
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine.|Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes National Primate Research Center, Atlanta, GA.|Howard Hughes Medical Institute, Bethesda, MD.
authors.forename: K J
authors.initials: KJ
authors.lastname: Ressler
authors.affiliation: Department of Pharmacology and Physiology, The George Washington University School of Medical and Health Sciences, Washington, DC, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Marvar
mesh_terms: D000818:Animals; D003214:Conditioning, Classical; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D005239:Fear; D046352:Freezing Reaction, Cataleptic; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*
chemical_list: C544066:Agtr1a protein, mouse; D044140:Receptor, Angiotensin, Type 1; D003346:Corticotropin-Releasing Hormone
keywords: Amygdala; PTSD; angiotensin II; angiotensin II receptor type 1; blood pressure; cardiovascular; corticotropin-releasing factor; extinction; fear; paraventricular nucleus