Role of the nucleus accumbens in regulating aggression reward.

伏隔核在调节攻击性奖赏中的作用。

基本信息

批准号：
9035528
负责人：
Sam Golden
金额：
--
依托单位：
U.S. NATIONAL INSTITUTE ON DRUG ABUSE
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：
2015-10-01 至 2018-10-01
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9035528
关键词：
Address Affective Affective Symptoms Aggressive behavior Autistic Disorder Behavior Behavioral Behavioral Model Body Regions Brain Calcium Cells Data Development Disease Dopamine Receptor Exhibits Exposure to Globus Pallidus Hypothalamic structure Image In Situ Individual Interdisciplinary Study Knowledge Label Lead Mediating Mental Depression Mental disorders Methodology Methods Modeling Molecular Moods Mus Neurobiology Neurons Nucleus Accumbens Pathway interactions Population Procedures Psychiatric Diagnosis RNA analysis Recruitment Activity Research Rewards Risk Role Series Social Behavior Social Interaction Stimulus System Techniques Testing Therapeutic Tracer Training Ventral Tegmental Area Violence Viral activity marker awake base calcium indicator cell type combinatorial designer receptors exclusively activated by designer drugs experience male mouse model neural circuit neuropsychiatric disorder novel preference public health relevance research study response reward circuitry reward processing social success symptomatology

项目摘要

DESCRIPTION (provided by applicant): There is an increased risk for abnormal social behavior in individuals suffering from psychiatric disorders. Unfortunately, while many therapeutic strategies exist to treat such disorders, success rates are surprisingly low regardless of the psychiatric diagnosis. Perhaps less surprising, social disorders such as depression and autism often share common affective symptomatology, including misattributed or maladaptive aggressive behavior, yet it is unclear what neural circuits underlie this shared behavioral feature. Several disparate lines of research now suggest that maladaptive aggression may be caused by dysregulation of brain reward circuitry. Further, even in its non-pathological form, it i accepted that aggression itself can be reinforcing. Despite this evidence, our current understanding of the neurobiological basis of the rewarding component of aggressive behavior is limited. The broad objective of this proposal is to investigate how brain reward circuitry modulates aggression reward. This research will focus on the nucleus accumbens, a key node in brain reward circuitry, which has previously been implicated in regulating social reward and aversion. In order to directly address the connection between aggression and reward we will use a novel behavioral model that is based on aggression conditioned place preference (CPP). In this model, aggressive repeated inter-male social interactions with subordinate intruders in a distinct context lead to th development of aggression CPP to the aggression-paired context. Through a multidisciplinary research plan that utilizes molecular techniques, awake-behaving deep-brain calcium imaging, and chemogenetic manipulations, we will explore the role of the nucleus accumbens direct pathway (dopamine receptor type 1 expressing medium spiny neurons) and indirect pathway (dopamine receptor type 1 expressing medium spiny neurons) projections in regulating aggression reward. We hypothesize that these molecularly defined subpopulations within the NAc are differentially recruited for encoding aggression reward, and that the indirect pathway may be preferentially engaged within aggressive mice exhibiting CPP behavior. Preliminary data demonstrate that the nucleus accumbens is activated by intruder presentations in aggressive, but not non-aggressive, mice; further, expression of aggression CPP is modulated in aggressive mice by a Drd2- anatognist. This series of studies seeks to mechanistically identify how these distinct neuronal populations are differentially recruited for encoding aggression reward, and how these neurons mediate the long-lasting effects on aggression reward experience.

描述（由申请人提供）：患有精神疾病的个体出现异常社会行为的风险增加，不幸的是，尽管存在许多治疗此类疾病的治疗策略，但成功率却出人意料地低。也许不那么令人惊讶的是，抑郁症和自闭症等社会疾病通常具有共同的情感症状，包括错误归因或适应不良的攻击行为，但目前尚不清楚这种共同行为特征背后的神经回路是什么。适应不良的攻击性可能是由大脑奖赏回路失调引起的。此外，即使是非病理性的，我也承认攻击性本身可以增强，尽管有这些证据，但我们目前对攻击性神经生物学基础的理解。该提案的总体目标是研究大脑奖励电路如何调节攻击性奖励。这项研究将重点关注伏隔核，这是大脑奖励回路中的一个关键节点，它以前与调节社会奖励和厌恶有关。为了直接解决攻击性和奖励之间的联系，我们将使用一种基于该模型的新颖行为模型。在该模型中，通过利用分子的多学科研究计划，在特定背景下与下级入侵者进行侵略性重复的男性间社会互动导致攻击性 CPP 发展为攻击配对背景。技术、清醒行为深部脑钙成像和化学遗传学操作，我们将探讨伏隔核直接通路（表达中型多巴胺受体 1 型中型多棘神经元）和间接通路（表达中型多巴胺受体 1 型多巴胺神经元）预测的作用我们勇敢地说，NAc 内的这些分子定义的亚群是有差异地招募来编码攻击性奖励的，并且间接途径可能优先参与表现出 CPP 行为的攻击性小鼠。数据表明，攻击性而非非攻击性小鼠的入侵者表现会激活伏隔核；此外，攻击性 CPP 的表达是由 Drd2- 解剖学家调节的。神经元群体被差异性地招募来编码攻击性奖励，以及这些神经元如何介导对攻击性奖励体验的长期影响。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Compulsive Addiction-like Aggressive Behavior in Mice.

小鼠的强迫性成瘾样攻击行为。

DOI：
发表时间：
2017-08-15
期刊：
影响因子：
10.6
作者：
Golden, Sam A;Heins, Conor;Venniro, Marco;Caprioli, Daniele;Zhang, Michelle;Epstein, David H;Shaham, Yavin
通讯作者：
Shaham, Yavin

Nucleus Accumbens Drd1-Expressing Neurons Control Aggression Self-Administration and Aggression Seeking in Mice.

表达 Drd1 的伏隔核神经元控制小鼠的攻击自我管理和攻击寻求。