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We examined central nervous system (CNS), behavioral, endocrine, cardiac, and hepatic outcomes in male or female C57Bl\/6 mice subjected to chronic social stress (56\u2009days of social isolation, with intermittent social confrontation encounters twice daily throughout the final 20\u2009days). Females exhibited distinct physiological and behavioral changes, including relative weight loss, and increases in coronary resistance, hepatic inflammation, and thigmotaxic behavior in the open field. Males evidence reductions in coronary resistance and cardiac ischemic tolerance, with increased circulating and hippocampal monoamine levels and emerging anhedonia. Shared CNS gene responses include reduced hippocampal\n                    <jats:italic>Maoa<\/jats:italic>\n                    and increased\n                    <jats:italic>Htr1b<\/jats:italic>\n                    expression, while unique responses include repression of hypothalamic\n                    <jats:italic>Ntrk1<\/jats:italic>\n                    and upregulation of cortical\n                    <jats:italic>Nrf2<\/jats:italic>\n                    and\n                    <jats:italic>Htr1b<\/jats:italic>\n                    in females; and repression of hippocampal\n                    <jats:italic>Drd1<\/jats:italic>\n                    and hypothalamic\n                    <jats:italic>Gabra1<\/jats:italic>\n                    and\n                    <jats:italic>Oprm<\/jats:italic>\n                    in males. Declining cardiac stress resistance in males was associated with repression of cardiac leptin levels and metabolic, mitochondrial biogenesis, and anti\u2010inflammatory gene expression. These integrated data reveal distinct biological responses to social stress in males and females, and collectively evidence greater biological disruption or allostatic load in females (consistent with propensities to stress\u2010related mood and cardiovascular disorders in humans). Distinct stress biology, and molecular to organ responses, emphasize the importance of sex\u2010specific mechanisms and potential approaches to stress\u2010dependent disease.\n                  <\/jats:p>","DOI":"10.1002\/jnr.25115","type":"journal-article","created":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T02:31:25Z","timestamp":1662345085000},"page":"2004-2027","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Sex\u2010specific behavioral, neurobiological, and cardiovascular responses to chronic social stress in mice"],"prefix":"10.1002","volume":"100","author":[{"given":"Tessa J.","family":"Helman","sequence":"first","affiliation":[{"name":"School of Pharmacy and Medical Sciences Griffith University  Southport Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Headrick","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Medical Sciences Griffith University  Southport Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Vider","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Medical Sciences Griffith University  Southport Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason N.","family":"Peart","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Medical Sciences Griffith University  Southport Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas J. 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