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Preclinical findings on the potential of intranasal neuropeptide Y for treating hyperarousal features of PTSD
Author(s) -
Nwokafor Chiso,
Serova Lidia I.,
Sabban Esther L.
Publication year - 2019
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.14172
Subject(s) - neuropeptide y receptor , locus coeruleus , startle response , fight or flight response , medicine , endocrinology , amygdala , neuropeptide , hypothalamus , nasal administration , psychology , receptor , central nervous system , pharmacology , biology , gene , biochemistry
Acoustic startle response (ASR) assesses hyperarousal, a core symptom of posttraumatic stress disorder (PTSD). Intranasal neuropeptide Y (NPY) administration was shown to prevent hyperarousal in single prolonged stress (SPS) rodent PTSD model. However, it is unclear how ASR itself alters responses to stress. Rats (A‐S‐A) were exposed to acoustic startle (AS) 1 day before SPS (ASR1) and 2 weeks afterward (ASR2). Other groups were exposed in parallel to either AS (A‐A) or SPS or neither. SPS enhanced ASR2. In relevant brain areas, mRNA levels were determined by qRT‐PCR. In mediobasal hypothalamus, AS or SPS each increased CRH mRNA levels without an additive effect. Exposure to AS appeared to dampen some responses to SPS. The SPS‐triggered reduction of GR and FKBP5 gene expression was not observed in A‐S‐A group. In locus coeruleus, SPS increased CRHR1 and reduced Y2R mRNAs, but not in A‐S‐A group. In both regions, AS altered NPY receptor gene expression, which may mediate dampening responses to SPS. In second experiment, intranasal NPY administered 2 weeks after SPS reversed hyperarousal symptoms for at least 7 days. This study reveals important effects of AS on the NPY system and demonstrates that intranasal NPY elicits long‐lasting reversal of traumatic stress–triggered hyperarousal.