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.

The expression level of muscarinic M1 receptor subtypes in different regions of rat brain

“…Therefore, in this study, for a stressor (predator scent) a dirty cat litter was used and a clean cat litter was used as a situational reminder. Like Cohen et al [22], also in this study it had been found out that the anxiety index was significantly higher in the stress group. Our data also demonstrated that the cat litter test was a reproducible experiment where the rats were subjected to a dirty cat litter had higher anxiety The expression level of muscarinic M 1 receptor subtypes in rat brain Marmara Medical Journal 2017; 30: [162][163][164][165][166][167][168] indexes when subjected to the clean cat litter, a situational reminder.…”

The effect of strategies of personal resilience on depression recovery in an Australian cohort: A mixed methods study

“…There is an emerging body of research examining biological markers for resilience, including glucocorticoid receptors (Wagner, Marinescu et al 2012) and neuropeptides (Kozlovsky, Matar et al 2009, Cohen, Liu et al 2012). …”

Understanding Resilience

“…Many studies on animal models and humans have confirmed the beneficial role of NPY in mediating resilience and vulnerability to stress and anxiety. Animals with PTSD-like behaviors showed a significant down-regulation of NPY in several brain regions including the amygdala and hippocampus, and centrally administered NPY reversed the negative behavioral effects of predator-scent stress (Cohen et al, 2012). Human studies found that, under uncontrollable stress induced by harsh military training, plasma NPY levels were markedly increased, and higher NPY levels were associated with better behavioral performance and stress response (Morgan et al, 2000(Morgan et al, , 2002.…”