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However, females are especially affected with greater vulnerability for substance use (SU) and adverse outcomes associated with pregnancy, including for offspring at birth and later in life. In mice, prenatal CRD (pCRD) recapitulates these risks, but it is unknown whether pCRD affects SU in mature offspring. To investigate this, C57BL\/6J dams were disrupted by reversing the light\/dark cycle during gestation. Following pCRD, reward- (cocaine conditioned place preference, intravenous self-administration) and mood-related behaviors (open field, elevated plus maze, light\/dark box, forced swim) were measured in adult offspring. Adult female offspring of dams exposed to CRD developed an anhedonic-like phenotype with decreased food self-administration, cocaine intake and reinforcing properties of cocaine. Opposingly, pCRD male offspring showed a SU-like phenotype with increased cocaine preference, higher order food self-administration and cocaine reinforcement. Interestingly, these divergent behavioral outcomes were not specific to reward. While female pCRD mice showed increased anxiety-like behavior, pCRD males showed decreased anxiety\/increased risk-taking behavior, as well as decreased immobility in the forced swim test. Rhythms in corticosterone were also sex-specifically affected by pCRD. These results suggest that pCRD may predispose individuals to distinct psychiatric disorders based on sex with mood disorders developing in females and SU disorders developing in males. By better understanding how disrupted rhythms during pregnancy affect behavior in adulthood, we can develop novel therapeutic approaches for SU and mood disorders in adults.<\/jats:p>","DOI":"10.64898\/2026.06.22.733807","type":"posted-content","created":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T15:35:13Z","timestamp":1782660913000},"source":"Crossref","is-referenced-by-count":0,"title":["Prenatal circadian rhythm disruption induces sex-specific substance use and mood-related phenotypes in mice"],"prefix":"10.64898","author":[{"given":"Nilanjana","family":"Saferin","sequence":"first","affiliation":[{"name":"Department of Neurosciences and Psychiatry, University of Toledo, College of Medicine and Life Sciences, Toledo, OH, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Stowe","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Translational Neuroscience Program, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States"},{"name":"Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea A.","family":"Vadnie","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Translational Neuroscience Program, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States"},{"name":"Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, United States"},{"name":"David O. 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