title: Overexpression of corticotropin-releasing factor receptor type 2 in the bed nucleus of stria terminalis improves posttraumatic stress disorder-like symptoms in a model of incubation of fear.
abstract: BACKGROUND
  Posttraumatic stress disorder (PTSD) is a severe, persistent psychiatric disorder in response to a traumatic event, causing intense anxiety and fear. These responses may increase over time upon conditioning with fear-associated cues, a phenomenon termed fear incubation. Corticotropin-releasing factor receptor type 1 (CRFR1) is involved in activation of the central stress response, while corticotropin-releasing factor receptor type 2 (CRFR2) has been suggested to mediate termination of this response. Corticotropin-releasing factor (CRF) receptors are found in stress-related regions, including the bed nucleus of stria terminalis (BNST), which is implicated in sustained fear.
  
  
  METHODS
  Fear-related behaviors were analyzed in rats exposed to predator-associated cues, a model of psychological trauma, over 10 weeks. Rats were classified as susceptible (PTSD-like) or resilient. Expression levels of CRF receptors were measured in the amygdala nuclei and BNST of the two groups. In addition, lentiviruses overexpressing CRFR2 were injected into the medial division, posterointermediate part of the BNST (BSTMPI) of susceptible and resilient rats and response to stress cues was measured.
  
  
  RESULTS
  We found that exposure to stress and stress-associated cues induced a progressive increase in fear response of susceptible rats. The behavioral manifestations of these rats were correlated both with sustained elevation in CRFR1 expression and long-term downregulation in CRFR2 expression in the BSTMPI. Intra-BSTMPI injection of CRFR2 overexpressing lentiviruses attenuated behavioral impairments of susceptible rats.
  
  
  CONCLUSIONS
  These results implicate the BNST CRF receptors in the mechanism of coping with stress. Our findings suggest increase of CRFR2 levels as a new approach for understanding stress-related atypical psychiatric syndromes such as PTSD.
authors.affiliation: The Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan; The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan.
authors.forename: Einat
authors.initials: E
authors.lastname: Elharrar
authors.forename: Gal
authors.initials: G
authors.lastname: Warhaftig
authors.forename: Orna
authors.initials: O
authors.lastname: Issler
authors.forename: Yehezkel
authors.initials: Y
authors.lastname: Sztainberg
authors.forename: Yahav
authors.initials: Y
authors.lastname: Dikshtein
authors.forename: Roy
authors.initials: R
authors.lastname: Zahut
authors.forename: Lior
authors.initials: L
authors.lastname: Redlus
authors.forename: Alon
authors.initials: A
authors.lastname: Chen
authors.forename: Gal
authors.initials: G
authors.lastname: Yadid
mesh_terms: D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001526:Behavioral Symptoms / Q000523:psychology / Q000628:therapy; D004195:Disease Models, Animal; D005239:Fear / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D012686:Septal Nuclei / Q000378:metabolism*; D013313:Stress Disorders, Post-Traumatic / Q000523:psychology / Q000628:therapy*
chemical_list: D018019:Receptors, Corticotropin-Releasing Hormone
keywords: Anxiety; BNST; CRFR1; CRFR2; PTSD; fear