This translational, interdisciplinary investigation focuses on the neural circuitry involved in the initiation of early parental care in cocaine-abusing mothers using functional imaging. We focus especially on actively cocaine-dependent women because (1) cocaine abuse is highly correlated with maternal neglect of offspring and poorer maternal-infant interactions in both human and animal models;(2) cocaine addiction co-opts neural circuitry recently shown key to early parenting in both preclinical and human models, that is, dopaminergically regulated limbic-hypothalamic-midbrain brain reward circuits, and (3) parallel studies of cocaine-exposure in the parturient rodent model point to specific disruptions in maternal sensitivity to offspring's cries, olfactory cues, tactile stimulation, and activity patterns such that mothers are more neglectful of their offspring. In this study, 75 cocaine-abusing, 75 non-drug-abusing, and 50 non-cocaine-abusing but other-drug-using, pregnant or recently delivered women will be recruited to participate at 2-4 weeks and 6 months postpartum in a neuroimaging study in which they will listen to cries of known spectral characteristics from cocaine-exposed and non-cocaine-exposed infants and view images of infants 0-6 months in potentially threatening situations. Mothers will rate the intensity of their emotional experience in response to each of the cries and images. At each session, women will be screened for cocaine and tobacco use through urine and serum toxicology. Salivary cortisol, peripheral oxytocin and prolactin levels will be collected pre and post imaging procedure. At 6 months, mothers and infant will participate in a play interaction to examine the relation between parental behavior with the infant and the degree of activation in fear and attachment related circuitry. At two weeks only, cries will be recorded from infants using a standard procedure and analyzed for spectral characteristics, and serum will be obtained from mothers and buccal swabs from infants for DMA extraction and genotyping of relevant polymorphisms identified in preclinical studies as related to parental affiliation (dopamine beta hydroxylase, Fos B, prolactin, and oxytocin). Understanding the neural mechanisms critical to parental investment in infants will facilitate more refined earlier interventions during pregnancy and immediate postpartum period to help substance abusing parents provide sufficient care for their infant despite the compromises they may bring to their parenting role. Earlier and more sustained parental care of infants will also reduce the intergenerational impact of substance abuse on later risk for addiction and related psychopathology among adolescents and young adults.
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