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U.S.A."],"published-print":{"date-parts":[[2026,7,7]]},"abstract":"<jats:p>\n                    Although fear conditioning has elucidated cue-evoked acute fear responses, the mechanisms by which stress experiences induce generalized internal states linked to anxiety or phobia are poorly understood. Here, we report that robust stress induces a persistent behavioral change characterized by avoidance of a confined space, claustrophobia-like behavior (CLB) in\n                    <jats:italic toggle=\"yes\">Drosophila<\/jats:italic>\n                    . Unlike aversive memory formation, the development of CLB does not require dopamine receptors. Our neuronal screening determined that neuropeptide signaling via Allatostatin-A inactivates the downstream neurons via its receptor AstA-R1, causally inducing CLB. Moreover, gene expression profiling of individual fly heads revealed that innate immune response activation in the blood\u2013brain barrier is involved in CLB. Our data demonstrate that stress-induced persistent behavioral change would not be related to a canonical mechanism of aversive memory formation, rather involves neuropeptidergic signaling and the blood\u2013brain barrier, providing the mechanism determining internal states which persistently change into a phobia-like mode.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2517987123","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T17:41:20Z","timestamp":1782927680000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["Neuropeptide signaling and the blood\u2013brain barrier generate a persistent stress-induced internal state in\n                    <i>Drosophila<\/i>"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9165-842X","authenticated-orcid":false,"given":"Abdalla 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