Sex differences in oxytocin modulation of social reward in the mesolimbic dopamine system

催产素调节中边缘多巴胺系统社会奖励的性别差异

• 批准号: 9470027
• 负责人: Johnathan Borland
• 金额: $ 3.83万
• 依托单位: GEORGIA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-18 至 2019-09-17
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9470027
• 关键词: Agonist; Attenuated; Behavior; CRISPR/Cas technology; Data; Development; Dopamine; Female; Functional Magnetic Resonance Imaging; Functional disorder; Gene Targeting; Goals; Guide RNA; Hamsters; Human; Incidence; Injectable; Injection of therapeutic agent; Investigation; Knock-out; Knowledge; Lead; Maintenance; Mediating; Memory; Mental disorders; Mesocricetus auratus; Mutation; Neurons; Nucleus Accumbens; Oxytocin; Oxytocin Receptor; Pair Bond; Pharmacology; Play; Positive Reinforcements; Prevalence; Process; Property; Psychiatric therapeutic procedure; RNA Probes; Regulation; Research Training; Rewards; Role; Same-sex; Sex Behavior; Sex Characteristics; Site; Social Behavior; Social Conditions; Social Interaction; Technology; Testing; Ventral Tegmental Area; Woman; base; behavior test; classical conditioning; design; experimental study; improved; knock-down; male; men; mesolimbic system; neural circuit; neuromechanism; novel; nuclease; paraventricular nucleus; preference; pressure; receptor; response; sex; small hairpin RNA; social; transcriptome

Abstract: The rewarding properties of social interaction are critical for the development of adaptive social relationships. Because the social behavior of males and females evolved in response to very different selective pressures the neural mechanisms mediating social behavior are likely sexually differentiated. A critical gap in our understanding of the mechanisms regulating the expression of social behavior is an understanding of the basic neural mechanisms underlying social reward, particularly in females. Dysfunctions in the mechanisms mediating social reward play a major role in many psychiatric disorders [1-3]. Furthermore, sex differences in the mechanisms mediating social reward likely contribute to the well known, but little understood sex differences in the prevalence of psychiatric disorders [10,11]. Therefore, the overall goal of this proposal is to investigate sex differences in the neural mechanisms mediating social reward. Although the neural circuitry mediating social reward has not been fully elucidated, an essential component is the mesolimbic dopamine system (MDS). Our lab has very recently shown that oxytocin (OT) receptors in the ventral tegmental area are essential for social reward in male hamsters. Several lines of evidence suggest the MDS is sexually differentiated and I now have strong preliminary data that OT injected into the VTA increases the rewarding properties of social interaction in males, but decreases the rewarding properties of social interaction in females. This proposal will critically test the overarching hypothesis that there are major sex differences in the neural mechanisms mediating social reward. More specifically, I propose that these sex differences in social reward are the result of sex differences in the effects of OT in the ventral tegmental area. The proposed studies will improve our understanding of sex differences in the mechanisms underlying social reward and will provide an outstanding opportunity for research training.

摘要： 社会互动的回报属性对于适应性社会关系的发展至关重要。因为 雄性和雌性的社会行为是在对非常不同的选择压力做出反应的过程中进化出来的， 调节社会行为的机制可能是性别差异的。我们对人类的理解 调节社会行为表达的机制是对基本神经机制的理解 潜在的社会奖励，尤其是女性。调节社会奖励机制的功能障碍 在许多精神疾病中起重要作用[1-3]。此外，性别差异的机制，调解社会 奖励可能有助于众所周知的，但很少了解的性别差异，在精神疾病的患病率 [10,11]第10,11话因此，本研究的总体目标是研究神经机制的性别差异 中介社会奖励。虽然调节社会奖励的神经回路尚未完全阐明，但 重要的组成部分是中脑边缘多巴胺系统（MDS）。我们的实验室最近发现，催产素（OT） 腹侧被盖区的受体对雄性仓鼠的社会奖励是必不可少的。若干条证据 我认为MDS是性分化的，我现在有强有力的初步数据表明OT注入VTA 增加了男性社会互动的奖励属性，但降低了社会互动的奖励属性。 女性的互动。这项提案将严格检验总体假设，即存在重大的性别差异 调节社会奖励的神经机制。更具体地说，我认为这些性别差异在社会中 奖赏效应是OT在腹侧被盖区作用的性别差异的结果。拟议的研究将 提高我们对社会奖励机制中性别差异的理解， 研究培训的绝佳机会。