Sex differences in mesolimbic dopamine responses to social stress

中脑边缘多巴胺对社会压力反应的性别差异

基本信息

批准号：
8503115
负责人：
BRIAN C TRAINOR
金额：
$ 37.33万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
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：
2013-06-27 至 2015-06-26
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8503115
关键词：
Agonist Animal Model Antibodies Anxiety Disorders Behavior Behavioral Brain California Cell Nucleus Collaborations Data Dopamine Dose Female Foundations Future Immunohistochemistry Label MAPK14 gene Manuscripts Mediating Mental Depression Mental disorders Modeling Modification Mood Disorders Mus Neurobiology Opioid Pharmacology Pilot Projects Population Process Property Psychosocial Stress Published Comment Rattus Receptor Signaling Research Risk Rodent Role Sex Characteristics Signal Pathway Social Interaction Stress Symptoms Testing Text Time Tyrosine 3-Monooxygenase Ventral Tegmental Area Withdrawal Woman Work base dopaminergic neuron dysphoria insight kappa opioid receptors male men mitogen-activated protein kinase p38 mouse model novel preference receptor function research study response sex social social organization social stress time use

项目摘要

Psychosocial stress is an important factor contributing to the onset of mood and anxiety disorders. Depression and anxiety disorders are more common in women than men, and there are important sex differences in responses to psychosocial stress. These data suggest that sex differences in responses to stress could mediate population-level sex differences in mental disorders. The social defeat paradigm reliably induces social withdrawal responses in animal models, a symptom that is present in both mood and anxiety disorders. However, a stumbling block to studying sex differences using this approach comes down to a simple problem. The most widely used rodent species have social organizations in which females are not aggressive towards each other. The basis for social defeat is physical confrontation. Thus, despite a steady drumbeat of ground breaking discoveries based on male mice and rats, there is a paucity of research on females. We study monogamous California mice, in which both males and females are aggressive. On average, females exposed to three episodes of social defeat show social withdrawal behavior whereas males do not. Kappa opioid receptors (KOR) function at the intersection of stress and depression-like behavior because they are activated during stress and can induce dysphoria. Studies in male mice suggest that the dysphoric effects of defeat stress are mediated in part by KOR activity. However, no study has ever tested this hypothesis in females. Preliminary data show that female California mice are, on average, more sensitive to the aversive properties of KOR than males. The proposed experiments test the hypothesis that sex differences in KOR activity contribute to sex differences in stress-induced social withdrawal. We also examine sex differences in KOR-dependent activation of p38 MAP kinase, which has been shown to mediate the aversive behavioral effects of KOR. The results of these experiments will provide novel insights into sex differences in the neurobiological and behavioral responses to social stress. Just in Time Information for 1R01MH097714-01A1 PI: Trainor, Brian C.

社会心理压力是导致情绪发作和的重要因素焦虑症。抑郁症和焦虑症在女性中比男人，对社会心理压力的反应存在重要的性别差异。这些数据表明，对压力反应的性别差异可以调解人群级别的性障碍性差异。社交失败范式可靠在动物模型中引起社交戒断反应，这是两者中存在的症状情绪和焦虑症。但是，研究性别差异的绊脚石使用这种方法归结为一个简单的问题。使用最广泛的啮齿动物物种有社会组织，其中女性对每个人都不是积极的其他。社交失败的基础是身体对抗。因此，尽管稳定基于雄性小鼠和大鼠的突破性发现的drumbeat，有一个对女性的研究很少。我们学习一夫一妻制的加利福尼亚小鼠男性和女性是积极进取的。平均而言，女性暴露于三集社交失败表明社交戒断行为，而男性则没有。 Kappa阿片类药物受体（kor）在压力和抑郁行为的交点上的功能因为它们在压力过程中被激活，并且会诱发烦躁不安。男性研究小鼠表明，失败压力的烦躁不安的影响部分由Kor介导活动。但是，没有研究在女性中检验了这一假设。初步数据表明雌性加利福尼亚小鼠平均对厌食症更敏感 Kor的特性比男性的特性。提出的实验检验了性别的假设 KOR活动的差异导致压力引起的社会性别差异提取。我们还检查了p38 MAP的KOR依赖性激活中的性别差异激酶已被证明可以介导Kor的厌恶行为影响。这这些实验的结果将提供有关性别差异的新见解神经生物学和行为对社会压力的反应。正好及时的信息1R01MH01MH097714-01A1 PI：Trainor，Brian C.

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Effects of kappa opioid receptors on conditioned place aversion and social interaction in males and females.

DOI：
10.1016/j.bbr.2014.01.003
发表时间：
2014-04-01
期刊：
BEHAVIOURAL BRAIN RESEARCH
影响因子：
2.7
作者：
Robles, Cindee F.;McMackin, Marissa Z.;Campi, Katharine L.;Doig, Ian E.;Takahashi, Elizabeth Y.;Pride, Michael C.;Trainor, Brian C.
通讯作者：
Trainor, Brian C.

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