Serotonin, Maternal Behavior and Postpartum Depression

血清素、母亲行为和产后抑郁症

基本信息

批准号：
8666818
负责人：
MING LI
金额：
$ 28.27万
依托单位：
UNIVERSITY OF NEBRASKA LINCOLN
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-06-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8666818
关键词：
Address Affect Agonist Amphetamines Animal Model Area Behavior Behavior Control Behavioral Behavioral Mechanisms Biological Neural Networks Caring Child Clozapine Combined Modality Therapy Complex Compulsive Hoarding Computer software Corpus striatum structure Development Dopamine Dose Drug Administration Routes Emotional Emotions Exhibits FOS gene Food Fright Goals HTR2A gene Health Human Incentives Infusion procedures Injection of therapeutic agent Knowledge Learned Helplessness Learning Light Link MK 212 Major Depressive Disorder Maternal Behavior Medial Mediating Memory Microarray Analysis Modeling Mothers Motivation Neurobiology Nucleus Accumbens Outcome Parenting behavior Pattern Performance Personal Satisfaction Pharmaceutical Preparations Pharmacology Play Postpartum Depression Postpartum Period Prefrontal Cortex Principal Investigator Process Psychotic Disorders Publishing Rattus Review Literature Rewards Role SB 242084 Sensory Receptors Serotonin Serotonin Receptor 5-HT2C Site Social Behavior Social Interaction System Techniques Testing Time Video Recording Work base behavior test design dopamine system effective intervention executive function innovation mesolimbic system neural circuit neurotransmission novel pre-clinical psychologic public health relevance pup receptor receptor function response

项目摘要

DESCRIPTION (provided by applicant): Maternal behavior in rats is a highly motivated and well-organized social behavior. It is an ecologically valid animal model for the study of basic psychological processes such as emotion, motivation, reward, learning and memory and social interaction, and has recently been used in modeling postpartum depression and psychosis. The core neural circuits underlying rat maternal behavior have been well elucidated. Recent work has also identified a role of the mesolimbic dopamine system in this behavior. However, considerably less is known about the role of serotonin (5-HT) in maternal care. Given the importance of serotonin in emotion, motivation, social behavior and major depression and its known interaction with dopamine, it is likely that functional disturbances of 5-HT systems would alter the quality of maternal care and may contribute to postpartum depression. One key issue remaining is to identify specific neuroreceptors and the underlying psychological processes through which serotonin act to affect maternal behavior. The Principal Investigator's long-term goal is to understand the behavioral mechanisms and neurobiological basis of maternal behavior. The objective of the proposed R01 project is to delineate the respective roles of 5-HT2A and 5-HT2C receptors in rat maternal behavior and identify their associated psychological processes. Based on preliminary studies and literature review, the Principal Investigator hypothesizes that disturbances of 5-HT2A and 5-HT2C receptor-mediated neurotransmission in the nucleus accumbens shell (NAs) and medial prefrontal cortex (mPFC)-related neural network disrupt maternal behavior. Because 5 -HT2A and 5-HT2C receptors play important yet opposing roles in incentive motivation, aversive processing, and executive controls, it is further hypothesized that activation or blockade of each 5-HT2 receptor alone disrupts maternal behavior. However, activation or blockade of both receptors concurrently will cause no or less disruption due to the antagonistic action between the two. Disturbances of 5-HT2A and 5-HT2C receptors cause maternal behavior deficits by decreasing maternal motivation, increasing negative emotional responses (e.g. fear, avoidance) toward pups, and/or fragmenting pup- directed responses. In the proposed study, Aim 1 will be to determine the effects of systemic injections of selective 5-HT2A and 5-HT2C agonists, antagonists, and their combinations on maternal behavior. Furthermore, the possible psychological processes (e.g. incentive motivation, fear responses, behavioral fragmentation) affected by 5-HT2A and 5-HT2C manipulations will be investigated. Aim 2 will be to determine the effects on maternal behavior of central infusions of these drugs - alone and in combination - into the NAs, mPFC and dorsolateral striatum. This project addresses an understudied area in maternal behavior. It is innovative in that behavioral, systemic and intracranial pharmacology approaches will be combined to comprehensively investigate the 5-HT receptor mechanisms involved in normal rat maternal behavior. It will help identify the behavioral processes linking altered maternal behavior and postpartum depression.

描述（由申请人提供）：大鼠的孕产妇行为是一种积极进取和组织良好的社会行为。它是一种具有生态有效的动物模型，用于研究基本的心理过程，例如情感，动机，回报，学习和记忆以及社交互动，并且最近已用于建模产后抑郁症和精神病。大鼠孕产妇行为的核心神经回路已得到很好的阐明。最近的工作还确定了中唇多巴胺系统在这种行为中的作用。但是，关于5-羟色胺（5-HT）在孕产妇护理中的作用知之甚少。鉴于5-羟色胺在情感，动机，社会行为和重大抑郁症及其与多巴胺的相互作用中的重要性，因此5-HT系统的功能障碍可能会改变产妇护理的质量，并可能导致产后抑郁症。剩下的一个关键问题是识别特定的神经感受器以及5-羟色胺作用影响孕产妇行为的基本心理过程。主要研究者的长期目标是了解孕产妇行为的行为机制和神经生物学基础。拟议的R01项目的目的是描述5-HT2A和5-HT2C受体在大鼠母体行为中的各自作用，并确定其相关的心理过程。基于初步研究和文献综述，主要研究者假设5-HT2A和5-HT2C受体介导的神经传递在伏隔核（NAS）和内侧前额叶皮层（MPFC）中相关的神经网络破坏母体行为中的障碍。由于5 -HT2A和5-HT2C受体在激励动机，厌恶处理和执行控制中起着重要但相反的作用，因此进一步假设，单独的每个5-HT2受体的激活或阻断会破坏母体行为。但是，由于两者之间的拮抗作用，同时对两个受体的激活或阻滞不会引起或多或少的破坏。 5-HT2A和5-HT2C受体的扰动通过减少母体动机，增加对幼犬的负面情绪反应（例如恐惧，避免）和/或分散的幼犬有向幼犬的反应来引起孕产妇行为缺陷。在拟议的研究中，目标1将是确定选择性5-HT2A和5-HT2C激动剂，拮抗剂及其对孕产妇行为的组合的影响。此外，将研究受到5-HT2A和5-HT2C操纵影响的心理过程（例如激励动机，恐惧反应，行为分裂）。 AIM 2将是确定对这些药物中心输注的孕产妇行为的影响 - 单独和组合 - 在NAS，MPFC和背外侧纹状体中的影响。该项目解决了孕产妇行为的研究领域。它具有创新性，因为将合并这种行为，系统性和颅内药理学方法，以全面研究与正常大鼠母体行为有关的5-HT受体机制。它将有助于确定链接改变母体行为的行为过程和产后抑郁症。