title: The neuropeptide Y (NPY)-ergic system is associated with behavioral resilience to stress exposure in an animal model of post-traumatic stress disorder.
abstract: Converging evidence implicates the regulatory neuropeptide Y (NPY) in anxiety- and depression-related behaviors. The present study sought to assess whether there is an association between the magnitude of behavioral responses to stress and patterns of NPY in selected brain areas, and subsequently, whether pharmacological manipulations of NPY levels affect behavior in an animal model of PTSD. Animals were exposed to predator-scent stress for 15 min. Behaviors were assessed with the elevated plus maze and acoustic startle response tests 7 days later. Preset cutoff criteria classified exposed animals according to their individual behavioral responses. NPY protein levels were assessed in specific brain regions 8 days after the exposure. The behavioral effects of NPY agonist, NPY-Y1-receptor antagonist, or placebo administered centrally 1 h post-exposure were evaluated in the same manner. Immunohistochemical technique was used to detect the expression of the NPY, NPY-Y1 receptor, brain-derived neurotrophic factor, and GR 1 day after the behavioral tests. Animals whose behavior was extremely disrupted (EBR) selectively displayed significant downregulation of NPY in the hippocampus, periaqueductal gray, and amygdala, compared with animals whose behavior was minimally (MBR) or partially (PBR) disrupted, and with unexposed controls. One-hour post-exposure treatment with NPY significantly reduced prevalence rates of EBR and reduced trauma-cue freezing responses, compared with vehicle controls. The distinctive pattern of NPY downregulation that correlated with EBR as well as the resounding behavioral effects of pharmacological manipulation of NPY indicates an intimate association between NPY and behavioral responses to stress, and potentially between molecular and psychopathological processes, which underlie the observed changes in behavior. The protective qualities attributed to NPY are supported by the extreme reduction of its expression in animals severely affected by the stressor and imply a role in promoting resilience and/or recovery.
authors: Anxiety and Stress Research Unit, Beer-Sheva Mental Health Center, The State of Israel Ministry of Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. hagitc@bgu.ac.il
authors: Hagit
authors: H
authors: Cohen
authors: Tianmin
authors: T
authors: Liu
authors: Nitsan
authors: N
authors: Kozlovsky
authors: Zeev
authors: Z
authors: Kaplan
authors: Joseph
authors: J
authors: Zohar
authors: Aleksander A
authors: AA
authors: Mathé
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009478:Neuropeptide Y / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D055500:Resilience, Psychological; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D013315:Stress, Psychological / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D001120:Arginine; C117416:BIBO 3304