Synaptic Sex Differences in the Nucleus Accumbens

伏隔核的突触性别差异

• 批准号: 7546692
• 负责人: PAUL M. FORLANO
• 金额: $ 5.13万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7546692
• 关键词: Addictive Behavior; Address; Adult; Area; Behavior; Brain; Characteristics; Chromosome Pairing; Confocal Microscopy; Dopamine; Drug Addiction; Drug Exposure; Electron Microscopy; Excitatory Synapse; Female; Food; Glutamate Transporter; Glutamates; Goals; Health; Immunofluorescence Immunologic; Label; Light; Link; Measures; Neural Pathways; Neurons; Nucleus Accumbens; Numbers; Partner in relationship; Quality of life; Rattus; Relapse; Research; Resources; Rewards; Sex Characteristics; Structure; Synapses; Testing; Tyrosine 3-Monooxygenase; Varicosity; Vertebral column; Woman; addiction; base; density; drug of abuse; immunocytochemistry; insight; male; men; nerve supply; neural circuit; neurochemistry; relating to nervous system; sexual dimorphism; spatial relationship

DESCRIPTION (provided by applicant): The neural circuitry of reward is an evolutionary conserved and adaptive mechanism which functions to reinforce the acquisition of essential resources, such as food and mates for species survival. Drugs of abuse hijack these same neural pathways, and continued use leads to addiction, the detriment of health and life quality, and in some cases, a permanent change in brain structures. Ample evidence exists for females to become addicted more quickly and have a greater propensity for relapse than males to drugs of abuse. However, no studies have addressed if pre-existing sexual dimorphisms exist in the structure of circuits underlying this behavior. The goal of this research is to investigate a potential neuroanatomical substrate for sex differences in addiction-related behaviors. I will quantify synaptic and neurochemical characteristics in the nucleus accumbens (NAc), an integral link in the neural circuitry of reward and addiction. My hypothesis is that NAc neurons in females not only receive greater excitatory input than males but also contain greater numbers of dopaminergic contacts in relation to excitatory inputs that may facilitate the action of dopamine during drug exposure. I will test this hypothesis by using light and electron microscopy to quantify numbers of excitatory synapses, glutamatergic input, and dopamine-positive varicosities containing or contacting excitatory synapses in male and female adult rats. While the major brain areas involved in drug addiction are well characterized, few studies have addressed why women are more prone to addiction than men. This research will provide new insights about the neural basis for sex differences in addictive behaviors.

描述（由申请人提供）：奖赏的神经回路是一种进化保守和适应性机制，其功能是加强对必要资源的获取，如食物和物种生存的配偶。滥用药物会劫持这些相同的神经通路，持续使用会导致成瘾，损害健康和生活质量，在某些情况下，大脑结构会发生永久性变化。有充分的证据表明，与男性相比，女性更容易对滥用药物上瘾，而且更容易复发。然而，没有研究表明，这种行为背后的电路结构中是否存在预先存在的性二态性。本研究的目的是探讨成瘾相关行为性别差异的潜在神经解剖学基础。我将量化突触和神经化学特性的神经核（NAc），在奖励和成瘾的神经回路的一个组成部分。我的假设是，NAC神经元在女性不仅收到更大的兴奋性输入比男性，但也包含更多的多巴胺能接触兴奋性输入，可能有利于多巴胺的作用在药物暴露。我将测试这一假设，通过使用光学和电子显微镜，以量化的兴奋性突触的数量，多巴胺能输入，多巴胺阳性静脉曲张包含或接触兴奋性突触在男性和女性成年大鼠。虽然涉及药物成瘾的主要大脑区域已经得到了很好的描述，但很少有研究能够解释为什么女性比男性更容易成瘾。这项研究将为成瘾行为性别差异的神经基础提供新的见解。