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

• Published in: European neuropsychopharmacology Vol. 28; no. 1; pp. 159 - 170
• Main Authors: Cohen, Hagit, Vainer, Ella, Zeev, Kaplan, Zohar, Joseph, Mathé, Aleksander A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2018
• Subjects: Adaptation, Psychological - drug effects; Adaptation, Psychological - physiology; Animal model; Animals; Basolateral Nuclear Complex - drug effects; Basolateral Nuclear Complex - metabolism; Basolateral Nuclear Complex - pathology; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Corticosterone - blood; Disease Models, Animal; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - pathology; Male; Neuropeptide S; Neuropeptide Y; Neuropeptide Y-Y1 receptor; Neuropeptides - metabolism; Post-traumatic Stress Disorder (PTSD); Rats, Sprague-Dawley; Receptors, Neuropeptide - antagonists & inhibitors; Receptors, Neuropeptide - metabolism; Receptors, Neuropeptide Y - antagonists & inhibitors; Receptors, Neuropeptide Y - metabolism; Resilience; Stress Disorders, Post-Traumatic - metabolism; Stress Disorders, Post-Traumatic - pathology; Stress Disorders, Post-Traumatic - psychology; Stress, Psychological - metabolism; Vulnerability; Neuropeptide Y; Animal model; Brain-derived neurotrophic factor; Neuropeptide S; Neuropeptide Y-Y1 receptor; Post-traumatic Stress Disorder (PTSD); Vulnerability; Resilience
• ISSN: 0924-977X; 1873-7862; 1873-7862
• DOI: 10.1016/j.euroneuro.2017.11.006

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.