Sex-dependent regulation of social reward by oxytocin in the mesolimbic reward circuitry

中脑边缘奖励回路中催产素对社会奖励的性别依赖性调节

基本信息

批准号：
10380844
负责人：
H. Elliott Albers
金额：
$ 55.05万
依托单位：
GEORGIA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-06 至 2026-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10380844
关键词：
Clinical Clustered Regularly Interspaced Short Palindromic Repeats Data Development Disease Dopamine Dose Female Gender Goals Hamsters Hypothalamic structure Incidence Knowledge Lateral Maintenance Measures Medial Mediating Mesocricetus auratus Neurodevelopmental Disorder Neurons Nucleus Accumbens Oxytocin Oxytocin Receptor Periodicity Prefrontal Cortex Prevalence Property Publishing Receptor Activation Regulation Rewards Rodent Role Same-sex Scanning Series Sex Differences Site Social Behavior Social Interaction Social Values Stimulus Symptoms System Testing Translations Ventral Tegmental Area base dopamine system drug of abuse improved male mesolimbic system neural circuit neurochemistry neuromechanism neuropsychiatric disorder novel preference pressure receptor response reward circuitry sex small hairpin RNA social social relationships

项目摘要

PROJECT SUMMARY The rewarding properties of social interactions are critical to the expression of adaptive social behavior and to the development and maintenance of social relationships. Little is known, however, about the factors that determine the reward value of social interactions or about the basic neural mechanisms that underlie social reward, particularly in females. We do know that the mesolimbic dopamine system (MDS) is central to the neural circuitry controlling the rewarding properties of many other stimuli such as drugs of abuse. A primary component of the MDS is dopamine (DA)-containing neurons in the ventral tegmental area (VTA) that project to the nucleus accumbens (NAc) as well as to other sites such as the medial prefrontal cortex. Critical inputs to the MDS include oxytocin (OT)-containing projections from the hypothalamus. We and others have demonstrated that, in male rodents, activation of OT receptors in the caudal VTA and in the NAc is essential for the rewarding properties of social interaction. Remarkably, despite the considerable evidence for sex differences in OT regulation of social behaviors, the role of OT in regulating social reward in females has not been investigated. This project will provide substantial new information on the factors that determine the reward value of social interactions and on the neural mechanisms that mediate social reward by testing this series of integrated hypotheses in male and female Syrian hamsters. Based on published and preliminary data from our lab and others, we have hypothesized that: 1) there is an inverted U relationship between the “dose” of social interactions and social reward, 2) this dose-response relationship is initiated at lower doses in females than in males, and 3) this sex difference is mediated by differential OT-induced DA release in the MDS. This project has substantial potential for translation to clinically-related problems by providing: 1) new information on how social stimuli can transition from being rewarding to being less rewarding or even aversive, 2) potential mechanisms for understanding well-known sex differences in the incidence of neuropsychiatric and neurodevelopmental disorders for which dysfunctional social relationships are an important symptom, and 3) the potential for development of gender- specific treatments for these disorders.

项目概要社交互动的奖励特性对于适应性社交行为的表达和然而，对于社会关系的发展和维持的因素却知之甚少。确定社交互动的奖励价值或社交背后的基本神经机制奖励，特别是在女性中，我们确实知道中边缘多巴胺系统（MDS）对于奖励至关重要。控制许多其他刺激（例如滥用药物）的奖励特性的神经回路。 MDS 的组成部分是腹侧被盖区 (VTA) 中含有多巴胺 (DA) 的神经元，它投射伏隔核（NAc）以及其他部位，例如内侧前额叶皮层。 MDS 包括来自下丘脑的含有催产素 (OT) 的投射。证明，在雄性啮齿动物中，尾侧 VTA 和 NAc 中 OT 受体的激活是值得注意的是，尽管有相当大的影响，但它对于社交互动的有益特性至关重要。 OT 调节社会行为中性别差异的证据，OT 在调节社会奖励中的作用该项目将提供有关影响因素的大量新信息。确定社交互动的奖励价值以及调节社会奖励的神经机制通过在雄性和雌性叙利亚仓鼠中测试这一系列综合假设。以及我们实验室和其他实验室的初步数据，我们发现：1）存在倒 U 社会互动的“剂量”和社会奖励之间的关系，2）这种剂量反应女性中的关系起始剂量低于男性，并且 3）这种性别差异是介导的通过 MDS 中差异 OT 诱导的 DA 释放该项目具有巨大的转化潜力。通过提供以下内容来解决临床相关问题：1）关于社会刺激如何从社会刺激转变为社会刺激的新信息奖励转为奖励较少甚至厌恶，2）理解众所周知的潜在机制神经精神和神经发育障碍的发病率存在性别差异功能失调的社会关系是一个重要症状，3）性别发展的潜力针对这些疾病的具体治疗方法。