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We previously demonstrated that intranasal delivery of the Y1R-selective analog D[His\n                    <jats:sup>26<\/jats:sup>\n                    ]NPY at the time of trauma induced by Single Prolonged Stress (SPS), a validated rodent model for post-traumatic stress disorder (PTSD), effectively prevented stress-induced behavioral impairments in male rats. D[His\n                    <jats:sup>26<\/jats:sup>\n                    ]NPY was more effective than either intranasal administration of native NPY or the Y1R agonist [Leu\n                    <jats:sup>31<\/jats:sup>\n                    Pro\n                    <jats:sup>34<\/jats:sup>\n                    ]NPY. In females, who are more susceptible to stress-related anxiety disorders and PTSD, native NPY has shown limited efficacy. Here, we investigated: (1) efficacy of intranasal D[His\n                    <jats:sup>26<\/jats:sup>\n                    ]NPY in female rats; (2) time-dependence of intranasal administration of D[His\n                    <jats:sup>26<\/jats:sup>\n                    ]NPY effectiveness for males, in preventing or reversing behavioral impairments. Our results revealed that in female rats, D[His\n                    <jats:sup>26<\/jats:sup>\n                    ]NPY produced robust anxiolytic effects at lower doses than native NPY. In male rats, intranasal D[His\n                    <jats:sup>26<\/jats:sup>\n                    ]NPY administered at the time of trauma, or 1\u00a0day before, averted the development of SPS-induced anxiety and social interaction deficits. Even when given two days prior to the traumatic stress intranasal D[His\n                    <jats:sup>26<\/jats:sup>\n                    ]NPY was partiallly effective. However, in contrast to native NPY, D[His\n                    <jats:sup>26<\/jats:sup>\n                    ]NPY failed to reverse the established behavioral impairments, when administered two weeks after SPS. These findings suggest that despite sex-specific differences, nose to brain delivery of the Y1R agonist D[His\n                    <jats:sup>26<\/jats:sup>\n                    ]NPY could be especially useful as a prophylactic treatment to prevent long-term adverse harmful effects of traumatic stress in both males and females.\n                  <\/jats:p>","DOI":"10.1007\/s00213-026-07044-5","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T08:18:15Z","timestamp":1773908295000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["D[His26]NPY, an agonist of NPY receptor 1, averts traumatic stress-induced behavioral deficits in male and female rats"],"prefix":"10.1007","author":[{"given":"Arax","family":"Tanelian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bistra","family":"Nankova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moshe","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther L.","family":"Sabban","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"issue":"5943","key":"7044_CR1","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1038\/306584a0","volume":"306","author":"TE Adrian","year":"1983","unstructured":"Adrian TE, Allen JM, Bloom SR, Ghatei MA, Rossor MN, Roberts GW, Crow TJ, Tatemoto K, Polak JM (1983) Neuropeptide Y distribution in human brain. 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