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Cocaine use by human mothers during pregnancy is highly correlated with child neglect, maternal anxiety and depression. Human and rodent infants exposed to cocaine in utero exhibit altered behavioral and neurological phenotypes, and appear to be less able to elicit normal care from biological and foster mothers. In rodents, specific pup-produced stimuli, including vocalizations, olfactory cues, and body temperature, have been associated with the initiation and maintenance of maternal response. Animal models indicate that chronic cocaine (CC) treatment throughout gestation disrupts postpartum maternal behavior (MB), including retrieving pups to the nest, nursing and licking behaviors, while simultaneously altering oxytocinergic signaling (receptors, levels, synthesis). It has not yet been determined if plasma levels of OT in rodents are also altered by CC treatment or if they are associated with brain region-specific changes. The current studies found that gestational cocaine exposure alters the retrieval behavior of dams in an interactive manner depending on dam treatment, pup treatment and postpartum day tested. On PPD5, CC-treated dams were found to have lower plasma OT, without differing in brain OT following a retrieval test. Group pup ultrasonic vocalizations did not differ significantly between prenatal exposure conditions, indicating these may not be the most relevant cues by which dams differentiate between litters. In addition to changes in response to pups, CC treatment resulted in disrupted stress-coping that was associated with increased hormonal stress responsiveness and changes in brain OT levels, both of which could be a mechanism of altered maternal response. Olfactory preference for pup urine declined across the postpartum period and only CC-treated dams specifically avoided CC-exposed pup urine olfactory cues. The complex nature of maternal-infant interactions during the early postpartum period was clear in this study, highlighting the need for continued studies to pinpoint the underlying mechanisms of cocaine-induced changes in dam maternal response and how early differential patterns of biological and behavioral measures in pups might further exacerbate disruptions in maternal care by any dam. Furthermore, these studies suggest that stress-responsiveness may be an important contributing factor to disruptions in cocaine-induced deficits in MB.