Neuropeptide S in the basolateral amygdala mediates an adaptive behavioral stress response in a rat model of posttraumatic stress disorder by increasing the expression of BDNF and the neuropeptide YY1 receptor

Eur Neuropsychopharmacol. 2018 Jan;28(1):159-170. doi: 10.1016/j.euroneuro.2017.11.006. Epub 2017 Nov 20.

Abstract

Neuropeptide S (NPS) is a regulatory peptide that has anxiolytic and arousal-promoting effects in rodents. We used an animal model of posttraumatic stress disorder (PTSD) to assess long-term behavioral effects of a single dose of NPS, microinjected into the basolateral amygdala (BLA) 1h following exposure to predator-scent stress (PSS). To elucidate the molecular mechanism by which NPS attenuates behavioral stress responses, expression levels of neuropeptide Y (NPY), NPY-Y1 receptor (NPY-Y1R), and brain-derived neurotrophic factor (BDNF) were evaluated in the hippocampus. The behavioral and molecular effects of NPS receptor antagonist (NPS-RA), NPY-Y1R antagonist (NPY-Y1RA), or both administered centrally were evaluated in the same manner. Circulating corticosterone levels were measured at different time points following PSS-exposure. Immediate post-exposure treatment with NPS had a marked protective effect; BLA microinfusion of NPS completely abolished the extreme behavioral response to PSS, restored the decreased expression of BDNF and, unexpectedly, PY-Y1R, but didn't affect the decreased expression of NPY. BLA microinfusion of both NPY-Y1RA and NPS-RA together had an additive effect, which completely prevented the anxiolytic effects of NPS in rats exposed to PSS and disrupted the expression of NPY-Y1R in the hippocampus following NPS infusion. It may therefore be hypothesized that NPS acts, directly or indirectly, on both the NPY-Y1R and NPS receptors and that the cross-talk between NPS and NPY-Y1R may be necessary for the anxiolytic effects of NPS post-exposure. The NPS system might thus contribute to a potential endogenous mechanism underlying the shift towards adaptive behavioral response and thereby might be relevant as a pharmacological target for attenuating stress-related sequelae.

Keywords: Animal model; Brain-derived neurotrophic factor; Neuropeptide S; Neuropeptide Y; Neuropeptide Y-Y1 receptor; Post-traumatic Stress Disorder (PTSD); Resilience; Vulnerability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Psychological / drug effects
  • Adaptation, Psychological / physiology*
  • Animals
  • Basolateral Nuclear Complex / drug effects
  • Basolateral Nuclear Complex / metabolism*
  • Basolateral Nuclear Complex / pathology
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Corticosterone / blood
  • Disease Models, Animal
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Male
  • Neuropeptides / metabolism*
  • Rats, Sprague-Dawley
  • Receptors, Neuropeptide / antagonists & inhibitors
  • Receptors, Neuropeptide / metabolism
  • Receptors, Neuropeptide Y / antagonists & inhibitors
  • Receptors, Neuropeptide Y / metabolism*
  • Stress Disorders, Post-Traumatic / metabolism*
  • Stress Disorders, Post-Traumatic / pathology
  • Stress Disorders, Post-Traumatic / psychology
  • Stress, Psychological / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • Neuropeptides
  • Receptors, Neuropeptide
  • Receptors, Neuropeptide Y
  • neuropeptide S, rat
  • neuropeptide Y-Y1 receptor
  • BDNF protein, human
  • Corticosterone