Amygdala-Dependent Fear Is Regulated by Oprl1 in Mice and Humans with PTSD

• DOI: 10.1126/scitranslmed.3005656
• Publication Date: 2013-06-05T18:34:42Z
• Authors: Raül Andero; Shaun P. Brothers; Tanja Jovanovic; Yen T. Chen; Hasib Salah-Uddin; Michael Cameron; Thomas D. Bannister; Lynn Almli; Jennifer S. Stevens; Bekh Bradley; Elisabeth B. Binder; Claes Wahlestedt; Kerry J. Ressler
• Keywords: Nociceptin receptor; NOP

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 aftermath trauma may decrease development PTSD. Using a mouse model dysregulated fear, we found altered expression within amygdala Oprl1 gene (opioid receptor-like 1), which encodes nociceptin (NOP)/orphanin FQ receptor (NOP-R). Systemic central infusion SR-8993, new highly selective NOP-R agonist, impaired fear memory consolidation. In humans, single-nucleotide polymorphism (SNP) OPRL1 is associated with self-reported history childhood PTSD symptoms (n = 1847) after traumatic event. This SNP also physiological startle measures discrimination magnetic resonance imaging analysis amygdala-insula functional connectivity. Together, these data suggest function, processing, symptoms. Further, our activation Oprl1/NOP interfere consolidation, implications for prevention