Gestational Stress and Oxytocin-Dopamine Interactions in New Mothers

新妈妈的妊娠应激和催产素-多巴胺相互作用

基本信息

批准号：
9131789
负责人：
BENEDETTA J LEUNER
金额：
$ 18.15万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-01 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9131789
关键词：
Adverse effects Affect Animal Model Behavior Behavioral Brain region Caring Characteristics Child Child Rearing Chronic Chronic stress Cognitive Development Disease Dopamine Emotional Epidemiologic Studies Etiology Exhibits Female Goals Health Human Hypothalamic structure Impairment Infant Lead Love Maternal Behavior Medial Medical Mental Health Middle Hypothalamus Mood Disorders Mothers Motivation Neurobiology Nucleus Accumbens Outcome Oxytocin Pathway interactions Perinatal Personal Satisfaction Postpartum Depression Postpartum Period Pregnancy Preoptic Areas Public Health Rattus Reporting Research Rewards Risk Risk Factors Rodent Signal Transduction Smoker Stress System Testing Time United States Ventral Tegmental Area Woman base caregiving depressive symptoms dopamine system improved insight maternal caregiving maternal depression mesolimbic system mortality motivated behavior neurobiological mechanism neurochemistry neuromechanism offspring paraventricular nucleus pregnant social tool

项目摘要

DESCRIPTION (provided by applicant): Postpartum depression is a debilitating disorder affecting an estimated 20% of new mothers making it one of the most prevalent mental health conditions in women. In addition to classical depressive symptoms, postpartum depression is accompanied by disrupted caregiving which can have long-lasting deleterious effects on offspring development. The long-term goal of this project is to identify the key brain regions and neurochemicals acting in those regions that are responsible for impaired caregiving in depressed mothers in order to better understand the etiology of such impairments and how they can be effectively treated. To achieve that goal, animal models that incorporate known risk factors for postpartum depression provide a valuable translational tool. Epidemiological studies have shown that chronic stress during pregnancy is a major risk factor for postpartum depression. Like humans, pregnant rodents exposed to chronic gestational stress exhibit increased depressive-like behaviors during the postpartum period along with deficits in maternal behavior. Thus, the objective in this application is to use gestational stress to mechanistically study parenting deficits that are characteristic of postpartum depression. In this regard, maternal care is a rewarding, motivated behavior that like other types of motivated behaviors, involves the mesolimbic dopamine (DA) system, particularly DA projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) shell. An increasing number of studies suggest that oxytocin (OT) circuits from the paraventricular nucleus (PVN) and medial preoptic area (mPOA) of the hypothalamus closely interact with the DA system to regulate mother-infant interactions. The central hypothesis of this proposal is that gestational stress diminishes the motivation to engage in maternal care through a disruption in OT-DA interactions. We will use behavioral, neuroanatomical and neurochemical approaches to test our central hypothesis in two Specific Aims. Aim 1 will determine the extent to which the adverse effects of gestational stress on maternal motivation and maternal care are associated with altered DA activity in the postpartum NAc. Aim 2 will examine the effects of gestational stress on OT and OT inputs to the mesolimbic DA system. In these aims, targeted pharmacological manipulations of DA and OT will also be employed to examine the extent to which stress-induced deficits in maternal care and maternal motivation can be reversed. The proposed research is significant because it will provide much needed insight into the fundamental neurobiological mechanisms underlying impaired maternal functioning associated postpartum depression.

描述（由适用提供）：产后抑郁症是一种使人衰弱的疾病，估计有20％的新妈妈使其成为女性最普遍的心理健康状况之一。除经典的抑郁症状外，产后抑郁症还伴随着干扰的护理，这可能会对后代发展产生持久的有害影响。该项目的长期目标是确定在那些负责拒绝母亲的护理受损的区域中起作用的关键大脑区域和神经化学家，以便更好地了解这种障碍的病因以及如何有效治疗。为了实现这一目标，结合了产后抑郁症的已知风险因素的动物模型提供了宝贵的翻译工具。流行病学研究表明，怀孕期间的慢性应激是产后抑郁症的主要危险因素。像人类一样，暴露于慢性妊娠应激的怀孕啮齿动物在产后时期增加了抑郁样行为，以及孕产妇行为的缺陷。这是该应用程序的目的是利用妊娠应力来机械研究产后抑郁症的特征的育儿定义。在这方面，母亲护理是一种有意义的动机行为，与其他类型的融合行为一样，涉及中唇多巴胺（DA）系统，尤其是从腹侧侧面侧面区域（VTA）到Accumbens（NAC）壳的DA投影。越来越多的研究表明，下丘脑的旁核核（PVN）和内侧前区域（MPOA）的氧气（OT）电路与DA系统紧密相互作用以调节母亲互动。该提议的核心假设是，妊娠压力减少了通过ot-da相互作用中断从事孕产妇护理的动机。我们将使用行为，神经解剖学和神经化学方法在两个特定目标中检验我们的中心假设。 AIM 1将确定妊娠应力对母体动机和母性护理的不利影响与产后NAC的DA活性改变有关。 AIM 2将检查妊娠应力对OT和OT输入对中边DA系统的影响。在这些目标中，还将采用针对DA和OT的有针对性的药物操纵，以检查应力引起的孕产妇护理和孕产妇动机的缺陷。拟议的研究之所以重要，是因为它将提供急需的洞察力，以了解与产后抑郁症相关的基本神经生物学机制。