PRENATAL COCAINE,SMOKING AND OXYTOCIN IN HUMANS

描述（由申请人提供）：本K01指导研究科学家发展奖申请提出了一个为期5年的培训和研究计划，旨在促进候选人作为独立研究者的成长，并促进将重点转移到转化研究的新领域。这条新的研究路线是基于动物研究，确定神经肽，催产素（OT）是建立哺乳动物正常母性行为的必要条件，并描述了围产期可卡因暴露导致的OT活动和母性行为的中断。短期目标是研究催产素、母婴依恋和人类产前可卡因使用之间的联系。培训目标是为候选人提供以下方面的新知识和测量技能：1)人类母婴依恋的发展，以及与产前可卡因相关的异常；2)可卡因成瘾和围产期滥用的神经生物学，重点是OT活动的失调；3)利用功能性磁共振成像（fMRI）识别涉及奖励、依恋和对婴儿线索反应的母亲脑回路的研究设计和实施培训。该培训将补充候选人在心血管和神经内分泌应激反应研究以及OT在人类社会互动中的作用的心理生理学研究方面的强大背景。该研究部分的具体目的是：1)对48名婴儿母亲（12名仅使用可卡因，12名可卡因+吸烟，12名仅使用吸烟，12名不使用药物）进行检查，产前暴露于可卡因和/或吸烟与母亲对实验室中有组织的母婴接触和实验压力源的行为和生理反应，以及与家庭环境中的行为和生理活动之间的关系；2)确定OT在这些反应中的作用；3)开展一项有监督的试点研究，利用功能磁共振成像（fMRI）来确定产前可卡因使用是否与涉及母体依恋和奖励的大脑感兴趣区域的不同激活有关，并将这些反应与OT水平联系起来。该MRSDA的发现将作为该奖项04-05年度R01申请的基础。拟议的研究、获得新技能和扩大跨学科范围将促进候选人建立独立研究事业的长期目标，研究人类社会依恋的生物学基础及其因滥用药物而改变。

DESCRIPTION (provided by applicant): 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.