TY - JOUR
T1 - Amygdala-dependent fear is regulated by Oprl1 in mice and humans with PTSD
AU - Andero, Raül
AU - Brothers, Shaun P.
AU - Jovanovic, Tanja
AU - Chen, Yen T.
AU - Salah-Uddin, Hasib
AU - Cameron, Michael
AU - Bannister, Thomas D.
AU - Almli, Lynn
AU - Stevens, Jennifer S.
AU - Bradley, Bekh
AU - Binder, Elisabeth B.
AU - Wahlestedt, Claes
AU - Ressler, Kerry J.
PY - 2013/6/5
Y1 - 2013/6/5
N2 - The amygdala-dependent molecular mechanisms driving the onset and persistence of posttraumatic stress disorder (PTSD) are poorly understood. Recent observational studies have suggested that opioid analgesia in the aftermath of trauma may decrease the development of PTSD. Using a mouse model of dysregulated fear, we found altered expression within the amygdala of the Oprl1 gene (opioid receptor-like 1), which encodes the amygdala nociceptin (NOP)/orphanin FQ receptor (NOP-R). Systemic and central amygdala infusion of SR-8993, a new highly selective NOP-R agonist, impaired fear memory consolidation. In humans, a single-nucleotide polymorphism (SNP) within OPRL1 is associated with a self-reported history of childhood trauma and PTSD symptoms (n = 1847) after a traumatic event. This SNP is also associated with physiological startle measures of fear discrimination and magnetic resonance imaging analysis of amygdala-insula functional connectivity. Together, these data suggest that Oprl1 is associated with amygdala function, fear processing, and PTSD symptoms. Further, our data suggest that activation of the Oprl1/NOP receptor may interfere with fear memory consolidation, with implications for prevention of PTSD after a traumatic event.
AB - The amygdala-dependent molecular mechanisms driving the onset and persistence of posttraumatic stress disorder (PTSD) are poorly understood. Recent observational studies have suggested that opioid analgesia in the aftermath of trauma may decrease the development of PTSD. Using a mouse model of dysregulated fear, we found altered expression within the amygdala of the Oprl1 gene (opioid receptor-like 1), which encodes the amygdala nociceptin (NOP)/orphanin FQ receptor (NOP-R). Systemic and central amygdala infusion of SR-8993, a new highly selective NOP-R agonist, impaired fear memory consolidation. In humans, a single-nucleotide polymorphism (SNP) within OPRL1 is associated with a self-reported history of childhood trauma and PTSD symptoms (n = 1847) after a traumatic event. This SNP is also associated with physiological startle measures of fear discrimination and magnetic resonance imaging analysis of amygdala-insula functional connectivity. Together, these data suggest that Oprl1 is associated with amygdala function, fear processing, and PTSD symptoms. Further, our data suggest that activation of the Oprl1/NOP receptor may interfere with fear memory consolidation, with implications for prevention of PTSD after a traumatic event.
UR - http://www.scopus.com/inward/record.url?scp=84880532753&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.3005656
DO - 10.1126/scitranslmed.3005656
M3 - Article
C2 - 23740899
AN - SCOPUS:84880532753
SN - 1946-6234
VL - 5
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 188
M1 - 188ra73
ER -