Neurobiological and Behavioral Consequences of Cocaine Use in Mother/Infant Dyads

描述（由申请人提供）：本项目是一个多学科、转化研究项目，采用动物和人类项目，重点阐明在怀孕期间主要使用可卡因的母亲的神经生物学和行为特征和反应，以及产前暴露于可卡因可能对正常母婴互动产生负面影响的后代。尽管在人类和动物模型中，母体可卡因的使用与母体忽视和较差的母婴互动高度相关，但很少有关于这些女性在看到相关婴儿线索（哭泣、触摸和图片）时的感知、内分泌和神经反应的直接研究。同样，对于婴儿产前暴露于可卡因的异常生理/行为反应，可能会影响吸毒和不吸毒母亲的养育行为，我们所知甚少。一个动物临床项目和两个人类临床项目将解决三个主要假设，即母亲使用可卡因和/或产前后代接触可卡因可能导致药物诱导的神经和/或生物行为异常，从而导致动物和人类的忽视和母婴互动不良。该动物项目将评估婴儿刺激或行为的特定特征（发声、体温调节能力、嗅觉线索、对母亲存在的反应）、大脑结构异常（区域、心室差异）和基因表达，以及测量母亲对暴露与未暴露婴儿或婴儿产生的刺激的不同行为和内分泌反应和偏好。人类项目将侧重于感知、内分泌和对压力相关和婴儿相关刺激的行为反应，以及婴儿对母亲的反应，以及婴儿大脑结构和通路发育异常（项目2）和（项目3）测量母亲（fMRI）内分泌和神经大脑区域对婴儿刺激的反应（哭闹，视觉小片段）。我们假设人类和啮齿类动物后代（产前药物暴露与非药物暴露）在行为、生理和/或神经学特征（婴儿哭声、婴儿刺激线索、身体护理和大脑结构异常）方面存在差异，这可能导致母体反应的差异。我们预测，与非吸毒者相比，滥用可卡因的母亲在感知、行为、内分泌和/或神经系统对相关婴儿刺激的反应方面会表现出差异。这一转化的跨学科项目将使具有不同研究背景和专业知识的研究人员能够共同努力，更好地确定母亲和婴儿的具体属性，从而有助于更好地了解具体滥用药物和一般个人的特定特征如何影响忽视。这可能导致早期和持续的干预策略，以抵消对这一人群的一些负面影响。

DESCRIPTION (provided by applicant): This program project is a multidisciplinary, translational research project employing animal and human projects to focus on the elucidation of neurobiological and behavioral characteristics and responses of mothers that have used primarily cocaine during pregnancy and of offspring prenatally exposed to cocaine that might impact negatively on normal mother-infant interactions. Although maternal cocaine use is known to be highly correlated with maternal neglect and poorer mother-infant interactions in both human and animal models, there is little direct research on perceptual, endocrine and neurological responses of these women when presented with relevant infant cues (cries, touch, and pictures). Similarly, little is known about abnormal physiological/behavioral responses in infants prenatally exposed to cocaine that may impact parenting behaviors of both drug using and non-using mothers. One animal, and 2 human clinical projects will address three main hypotheses which address the possibility that cocaine use by mothers and/or prenatal exposure to cocaine in offspring could result in drug-induced neurological and/or bio-behavioral abnormalities in both, that contribute to neglect and poor mother-infant interactions in animals and humans. The animal project will assess specific characteristics of infant stimuli or behavior (vocalizations, thermoregulatory ability, olfactory cues, response to mothers presence) and brain structural abnormalities (regional, ventricular differences) and gene expression as well as measuring differential maternal behavioral and endocrine responses to and preference for exposed compared to non-exposed infants or stimuli produced by infants. The human projects will focus on perceptual, endocrine and behavioral responses to stress related and infant related stimuli and infant response to mothers, as well as infant brain structural and pathway developmental abnormalities (project 2) and (project 3) measurement of maternal (fMRI) endocrine and neurological brain regional responses to infant stimuli (cries, visual vignettes). We hypothesize differences in behavioral, physiological and/or neurological characteristics (infant cries, infant stimulus cues, physical elicitation of care and brain structural abnormalities) of both human and rodent offspring (prenatally drug exposed versus non-exposed), which could result in differential maternal response. We predict that mothers who have abused cocaine will exhibit differences in perceptual, behavioral, endocrine and/or neurological responses to relevant infant stimuli compared to non-drug users. This translational, interdisciplinary project will allow researchers from different research backgrounds and expertise to work together to better identify specific attributes of mothers and infants that could contribute to a better understanding of how drugs of abuse specifically and particular characteristics of individuals in general may influence neglect. This could result in early and continuing intervention strategies to offset some of the negative consequences in this population. PROGRAM PROJECT CHARACTERISTICS