Neurobiological Control of Maternal Anxiety

母亲焦虑的神经生物学控制

基本信息

批准号：
8279263
负责人：
Joseph S Lonstein
金额：
$ 29.82万
依托单位：
MICHIGAN STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-31 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8279263
关键词：
Address Affect Agonist Amygdaloid structure Animal Model Animals Anti-Anxiety Agents Anxiety Anxiety Disorders Area Autoreceptors Behavior Bicuculline Biological Neural Networks Birth Brain Cell Nucleus Cells Child Cues Diagnosis Distal Down-Regulation Emotional Equilibrium Event FOS gene GABA Receptor Glutamates In Situ Hybridization Infant Infant Development Interneurons Knowledge Laboratory Rat Literature Mammals Measures Mediating Microdialysis Modeling Mothers Motivation Muscimol Neurobiology Neurons Norepinephrine Output Phenotype Postpartum Period Postpartum Women Prosencephalon Rattus Role Sensory Site Stimulus Structure of terminal stria nuclei of preoptic region System Tactile Testing Woman Work base experience extracellular falls gamma-Aminobutyric Acid improved in vivo insight interest male midbrain central gray substance nerve supply neurochemistry noradrenergic offspring postsynaptic prevent public health relevance receptor relating to nervous system research study response

Address Affect Agonist Amygdaloid structure Animal Model Animals Anti-Anxiety Agents Anxiety Anxiety Disorders Area Autoreceptors Behavior Bicuculline Biological Neural Networks Birth Brain Cell Nucleus Cells Child Cues Diagnosis Distal Down-Regulation Emotional Equilibrium Event FOS gene GABA Receptor Glutamates In Situ Hybridization Infant Infant Development Interneurons Knowledge Laboratory Rat Literature Mammals Measures Mediating Microdialysis Modeling Mothers Motivation Muscimol Neurobiology Neurons Norepinephrine Output Phenotype Postpartum Period Postpartum Women Prosencephalon Rattus Role Sensory Site Stimulus Structure of terminal stria nuclei of preoptic region System Tactile Testing Woman Work base experience extracellular falls gamma-Aminobutyric Acid improved in vivo insight interest male midbrain central gray substance nerve supply neurochemistry noradrenergic offspring postsynaptic prevent public health relevance receptor relating to nervous system research study response

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项目摘要

DESCRIPTION (provided by applicant): High maternal anxiety has tremendously detrimental effects on maternal motivation, mother-infant interactions, and infant development. Although a large number of women experience elevated anxiety after giving birth, the neurobiological events responsible for high postpartum anxiety or its alleviation are very poorly understood. Physical contact with infants can reduce anxiety in postpartum women and other mammals, and is vital for healthy maternal emotional states. I propose to investigate the neural basis of how contact with infants modulates maternal neurochemistry to reduce anxiety. I am specifically interested in the involvement of the ventral bed nucleus of the stria terminalis (vBST) and three of its primary targets (central amygdala, supramammillary nucleus, and periaqueductal gray), which are all traditional components of the neural network regulating anxiety. The vBST has one of the densest noradrenergic innervations of the forebrain, and high noradrenergic tone in the vBST is associated with high anxiety. This is likely due to altered GABAergic and glutamatergic output that directly or indirectly modulates downstream brain areas promoting anxiety. I propose that contact with infants is a natural stimulus chronically down-regulating noradrenergic tone in the vBST. This downregulation of vBST noradrenergic tone is proposed to increase local GABA release, which disinhibits GABAergic projections and/or inhibits glutamatergic projections from the vBST to widespread areas of the brain, resulting in reduced maternal anxiety. Using postpartum laboratory rats as a model, this hypothesis will be tested by: 1) examining the effects of pharmacologically increasing or decreasing noradrenergic tone in the vBST on mothers' anxiety-related behaviors, 2) using in vivo microdialysis to measure extracellular norepinephrine release in the vBST while mothers interact with infants or are exposed to particular sensory cues from their infants, 3) using anatomical tracing to determine the neurochemical phenotype (GABAergic or glutamatergic) of projections from the vBST and other BST subregions to the central amygdala, supramammillary nucleus, and periaqueductal gray and 4) pharmacologically manipulating GABAA receptor activity in these three vBST target sites to determine if GABAA receptor modulation in these areas can prevent or mimic the effects of infant contact on mothers' anxiety-related behaviors. These experiments will be the first to examine the role of norepinephrine in the vBST, and its larger neural network, in the anxiety-reducing effects of infant contact. This information will greatly reinforce the notion that physical contact with infants positively modulates maternal neurochemistry and emotional state, and will improve the diagnosis and treatment of the millions of women and their infants affected each year by postpartum anxiety disorders. PUBLIC HEALTH RELEVANCE: High postpartum anxiety has devastating effects on maternal motivation, mother-infant interactions, and infant development. Understanding the neural basis of how anxiety is regulated during the postpartum period is critically important for many women and their children. Determining how physical contact with infants modulates maternal neurochemistry in a way that alleviates anxiety will help improve the diagnosis and treatment of women suffering from a postpartum anxiety disorder.

描述（由申请人提供）：高产妇焦虑对孕产妇的动机，母性相互作用和婴儿发育产生巨大影响。尽管大量女性在分娩后经历了焦虑症，但对产后焦虑或缓解的神经生物学事件的理解很少。与婴儿的身体接触可以减轻产后妇女和其他哺乳动物的焦虑，并且对于健康的母性情绪状态至关重要。我建议研究与婴儿接触如何调节母体神经化学以减轻焦虑的神经基础。我特别对脊柱末端（VBST）的腹侧床核的参与特别感兴趣，其三个主要靶标（中央杏仁核，超氨基核和周围的灰色）都是神经网络调节焦虑的传统成分。 VBST具有前脑最密集的去甲肾上腺素能神经，VBST中的高肾上腺素能张力与高焦虑有关。这可能是由于GABA能和谷氨酸能的变化改变，该输出直接或间接地调节了促进焦虑的下游大脑区域。我建议与婴儿的接触是一种自然的刺激，在VBST中慢性下调的甲肾上腺素能。提出了VBST去甲肾上腺素能张力的这种下调，以增加局部GABA释放，这可以抑制GABA能预测和/或抑制谷氨酸能的投射，从VBST到大脑的广泛区域，从而降低了母亲的焦虑。 Using postpartum laboratory rats as a model, this hypothesis will be tested by: 1) examining the effects of pharmacologically increasing or decreasing noradrenergic tone in the vBST on mothers' anxiety-related behaviors, 2) using in vivo microdialysis to measure extracellular norepinephrine release in the vBST while mothers interact with infants or are exposed to particular sensory cues from their infants, 3）使用解剖学跟踪确定从VBST和其他BST子区域到中央杏仁核，超氨基核核，超膜核和周期灰色和4）的神经化学表型（GABA能或谷氨酸）的投影，以及这些三个V型GABAA受体模态，以确定这些三VBAA的gabaa受体的活性。区域可以预防或模仿婴儿接触对母亲焦虑相关行为的影响。这些实验将是第一个检查去甲肾上腺素在VBST及其更大的神经网络中的作用，在婴儿接触的焦虑减轻效果中的作用。这些信息将大大加强这样一种观念，即与婴儿的身体接触会对产妇神经化学和情绪状态进行正面调节，并将改善每年受产后焦虑症影响的数百万妇女及其婴儿的诊断和治疗。公共卫生相关性：产后焦虑症对孕产妇的动机，母亲互动和婴儿发育产生毁灭性影响。了解产后如何调节焦虑的神经基础对于许多妇女及其子女至关重要。确定与婴儿的身体接触如何以减轻焦虑的方式调节母体神经化学，将有助于改善患有产后焦虑症的妇女的诊断和治疗。