This K01 Mentored Research Scientist Development Award application proposes a 5-year program of training and research designed to promote the Candidate's growth as an independent investigator, and to facilitate a shift of focus to a new area of translational research. This new line of inquiry is based on animal studies that identify the neuropeptide, oxytocin (OT) as essential for establishment of normal maternal behaviors in mammals, and that describe the disruptions in both OT activity and maternal behavior resulting from perinatal cocaine exposure. The short-term objective is to examine links between oxytocin, mother infant attachment and prenatal cocaine use in humans. The training goals are to provide the Candidate with new knowledge and measurement skills in: 1) the development of human mother-infant attachment, and aberrations associated with prenatal cocaine, 2) the neurobiology of cocaine addiction and perinatal abuse with a focus on dysregulation of OT activity, 3) training in the design and implementation of studies utilizing functional magnetic resonance imaging (fMRI) to identify maternal brain circuitry involved in reward, attachment, and responses to infant cues. This training will complement the Candidate's strong background in cardiovascular and neuroendocrine stress reactivity research, and in psychophysiological study of the role of OT in human social interactions. The specific aims of the research component are: 1) to examine, in 48 mothers of infants (12 cocaine only, 12 cocaine + smoking, 12 smoking only, 12 no drug), how prenatal exposure to cocaine and/or smoking is linked to maternal behavioral and physiological responses to structured mother-infant contact and experimental stressors in the laboratory, and to behavioral and physiological activity in the home environment using ambulatory monitors and diaries;2) to determine the role of OT in these responses;and 3) to conduct a supervised pilot study, using fMRI to determine whether prenatal cocaine use is related to differential activation of brain regions of interest involved in maternal attachment and reward, and to relate these responses to OT levels. Findings from this MRSDA will be used as the basis of an R01 application in Years 04-05 of the award. The proposed research, acquisition of new skills, and expanded interdisciplinary scope will promote the Candidate's long-term goal of building an independent research career examining the biological basis of human social attachments and their alteration by drugs of abuse.
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