Prenatal Cocaine, Smoking And Oxytocin In Humans

描述(由申请者提供)：这份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一名独立研究人员的成长，并促进将重点转移到翻译研究的新领域。这一新的研究路线是基于动物研究，这些研究确定神经肽催产素(OT)是建立哺乳动物正常母体行为所必需的，并描述了围产期接触可卡因对催产素活动和母体行为的干扰。短期目标是检查催产素、母婴依恋和人类产前可卡因使用之间的联系。培训目标是为应聘者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)利用功能磁共振成像(FMRI)对研究的设计和实施进行培训，以确定与奖励、依恋和对婴儿暗示的反应有关的母亲大脑回路。这项培训将补充应聘者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。研究部分的具体目标是：1)调查48名婴儿的母亲(只吸食可卡因12人，吸食可卡因+吸食可卡因12人，不吸食毒品12人)，了解产前接触可卡因和/或吸烟与母亲在实验室中对结构性母婴接触和实验应激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的关系；2)确定催产素在这些反应中的作用；3)进行一项有监督的先导研究，使用功能磁共振成像来确定产前可卡因的使用是否与涉及母亲依恋和奖励的大脑感兴趣区域的差异激活有关，并将这些反应与催产素水平联系起来。这份MRSDA的调查结果将被用作该奖项04-05年度R01申请的基础。拟议的研究、新技能的获得和跨学科范围的扩大将促进候选人的长期目标，即建立一个独立的研究生涯，研究人类社会依恋的生物学基础及其被滥用药物改变的情况。

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.