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Preclinical experiments demonstrated that delivery of NPY by intranasal infusion to rats shortly after single exposure to traumatic stress in the single prolonged stress (SPS) rodent model of post\u2010traumatic stress disorder (PTSD) can prevent development of many relevant behavioral alterations weeks later, including heightened anxiety and depressive\u2010like behavior. Here, we examined responses to intranasal NPY in the absence of stress to evaluate the safety profile. Rats were administered intranasal NPY (150\u2009\u03bcg\/rat) or equal volume of vehicle (distilled water), and 7\u2009days later they were tested on the elevated plus maze (EPM) and forced swim test (FST). There was no significant difference in the number of entries or duration in the open or closed arms, or in their anxiety index. Defecation on the EPM and immobility on the FST, measures of anxiety and depressive\u2010like behavior respectively, were similar in both groups. To further characterize potential benefits of intranasal NPY, its effect on fear memory and extinction, important features of PTSD, were examined. Intranasal administration of NPY at the time of the traumatic stress had a profound effect on fear conditioning a week later. It prevented the SPS\u2010triggered impairment in the retention of extinguished behavior, both contextual and cued. The findings support the translation of non\u2010invasive intranasal NPY delivery to the brain for PTSD\u2010behaviors including impairments in sustained extinction of fear memories.<\/jats:p>","DOI":"10.1111\/jne.13279","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T19:24:44Z","timestamp":1682018684000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Potential benefits of intranasal neuropeptide Y include sustained extinction of fear memory"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6725-3235","authenticated-orcid":false,"given":"Esther L.","family":"Sabban","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology New York Medical College  Valhalla New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6232-7226","authenticated-orcid":false,"given":"Lidia","family":"Serova","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology New York Medical College  Valhalla New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roxanna J.","family":"Nahvi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology New York Medical College  Valhalla New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology New York Medical College  Valhalla New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,5,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/296659a0"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-7634(01)00066-5"},{"issue":"1","key":"e_1_2_9_4_1","first-page":"143","article-title":"XVI. 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