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The instability of maternal cues was used to model human separation anxiety in outbred mice, one of the etiopathogenetic factors that predict panic disorder (PD). Application of the repeated cross\u2010fostering (RCF) protocol to inbred strains (C57 and DBA) allowed us to measure differential responses to the same experimental manipulation. Ultrasounds emitted during isolation indicated that after RCF, pups from both strains lose their ability to be comforted by nest cues, but the frequency modulation of separation calls increased in RCF\u2010C57 and decreased in RCF\u2010DBA mice. No strain\u2010specific difference in olfactory ability explained these responses in RCF\u2010exposed mice. Rather, disruption of the infant\u2010mother bond may differentially affect separation calls in the two strains. Moreover, the RCF\u2010associated increased respiratory response to hypercapnia\u2013an endophenotype of human PD documented among mice outbred strains\u2013was replicated in the C57 strain only. We suggest that RCF\u2010induced instability of the early environment affects emotionality and respiratory physiology differentially, depending on pups\u2019 genetic background. These strain\u2010specific responses provide a lead to understand differential vulnerability to emotional disorders.<\/jats:p>","DOI":"10.1002\/dev.22135","type":"journal-article","created":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T02:07:19Z","timestamp":1625191639000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Mouse model of panic disorder: Vulnerability to early environmental instability is strain\u2010dependent"],"prefix":"10.1002","volume":"63","author":[{"given":"Alessandra","family":"Luchetti","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Cell Biology National Research Council, Monterotondo  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Di Segni","sequence":"additional","affiliation":[{"name":"Department of Psychology and Center \u201cDaniel Bovet,\u201d Sapienza University  Rome Italy"},{"name":"IRCCS Santa Lucia 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