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：
9041023
负责人：
MING LI
金额：
$ 29.54万
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/9041023
关键词：
Address Affect Agonist Amphetamines Animal Model Area Behavior Behavior Control Behavioral Behavioral Mechanisms Biological Neural Networks Caring Child Child Rearing 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 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 behavioral response design dopamine system effective intervention executive function innovation mesolimbic system neural circuit neurotransmission novel pre-clinical psychologic 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）：大鼠的母性行为是一种高度积极、组织良好的社会行为。它是一种生态上有效的动物模型，用于研究情绪、动机、奖励、学习和记忆以及社会互动等基本心理过程，最近已用于模拟产后抑郁症和精神病。大鼠母性行为的核心神经回路已得到很好的阐明。最近的研究还确定了中脑边缘多巴胺系统在这种行为中的作用。然而，人们对血清素 (5-HT) 在孕产妇护理中的作用知之甚少。鉴于血清素在情绪、动机、社会行为和重度抑郁症中的重要性及其与多巴胺的已知相互作用，5-HT 系统的功能紊乱很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确定特定的神经感受器以及血清素影响母亲行为的潜在心理过程。首席研究员的长期目标是了解母亲行为的行为机制和神经生物学基础。拟议的 R01 项目的目标是描述 5-HT2A 和 5-HT2C 受体在大鼠母性行为中各自的作用，并确定其相关的心理过程。根据初步研究和文献综述，首席研究员假设伏隔核壳 (NAs) 和内侧前额皮质 (mPFC) 相关神经网络中 5-HT2A 和 5-HT2C 受体介导的神经传递紊乱会扰乱母体行为。由于 5-HT2A 和 5-HT2C 受体在激励动机、厌恶处理和执行控制中发挥重要但相反的作用，因此进一步假设每种 5-HT2 受体的单独激活或阻断会破坏母体行为。然而，由于两者之间的拮抗作用，同时激活或阻断两种受体不会造成或较少造成破坏。 5-HT2A 和 5-HT2C 受体的紊乱会降低母性动机，增加对幼崽的负面情绪反应（例如恐惧、回避）和/或破坏幼崽定向反应，从而导致母性行为缺陷。在拟议的研究中，目标 1 将确定全身注射选择性 5-HT2A 和 5-HT2C 激动剂、拮抗剂及其组合对母亲行为的影响。此外，还将研究受 5-HT2A 和 5-HT2C 操纵影响的可能心理过程（例如激励动机、恐惧反应、行为碎片化）。目标 2 是确定这些药物（单独或联合）中枢输注至 NA、mPFC 和背外侧纹状体对母亲行为的影响。该项目涉及母亲行为中尚未得到充分研究的领域。其创新之处在于将行为、全身和颅内药理学方法相结合，全面研究参与正常大鼠母性行为的5-HT受体机制。它将有助于识别与母亲行为改变相关的行为过程和产后抑郁症。