Divergent Dopamine System Adaptions After Stress

压力后多巴胺系统的不同适应

• 批准号: 9396621
• 负责人: Zachary Brodnik
• 金额: $ 4.4万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9396621
• 关键词: AMPA Receptors; Alcohol or Other Drugs use; Animals; Anxiety; Behavior; Behavioral; Biological; Cells; Cocaine; Cocaine Abuse; Comorbidity; Cues; Data; Development; Disease; Dopamine; Electrophysiology (science); Event; Exhibits; Exposure to; Frequencies; Functional disorder; Glutamates; Goals; In Vitro; Individual; Injection of therapeutic agent; Link; Measurement; Measures; Membrane; Mental disorders; Microdialysis; Neurons; Nucleus Accumbens; Pathologic; Pathology; Periodicity; Permeability; Pharmaceutical Preparations; Phase; Phenotype; Physiological Adaptation; Physiology; Predisposition; Property; Rattus; Reporting; Scanning; Self Administration; Self-Administered; Signal Transduction; Source; Stress; Substance Use Disorder; Substance abuse problem; Testing; Tracer; Ventral Tegmental Area; Work; addiction; base; cocaine use; design; dopamine system; dopaminergic neuron; experience; experimental study; in vivo; mesolimbic system; neurochemistry; neuromechanism; neuronal cell body; resilience; response; segregation; selective expression; synaptic function; targeted treatment

Abstract Stress can trigger pathological changes in behavior and appears to augment substance abuse vulnerability. Nonetheless, only a portion of individuals who experience similar stress events develop any appreciable pathology, thus individuals may express either a susceptible or resilient phenotype following stress. Recent evidence suggests that susceptibility and resilience following stress are associated with distinct adaptations to the mesolimbic dopamine system, which is well known to participate in the development of substance use disorder. Whether increased substance use vulnerability selectively corresponds with the unique behaviors and physiology associated with susceptibility and resilience remains unknown. For our preliminary studies we exposed rats to predator scent stress, and segregated subjects as susceptible or resilient based on the context avoidance and heightened anxiety behavior in the elevated plus maze. Using this approach, we found that susceptibles but not resilients, display an increased propensity to self-administer cocaine. Further, we have identified that distinct dopamine system changes are associated with the susceptible phenotype. In combination with our preliminary studies, the proposed studies are designed to first determine the net effect of terminal and somatodendritic DA system alterations using in vivo measurements of DA activity, and second to isolate the sources of net changes in DA signaling by examining DA terminals or DA neuron soma independently.

摘要 压力可以引发行为的病理变化，似乎增加了药物滥用的脆弱性。 尽管如此，只有一部分经历过类似压力事件的人会出现明显的 因此，个体在应激后可能表现出易感或弹性表型。最近 有证据表明，压力后的易感性和恢复力与不同的适应有关， 中脑边缘多巴胺系统，这是众所周知的参与发展的物质使用 disorder.增加的物质使用脆弱性是否选择性地与独特的行为相对应， 与易感性和恢复力相关的生理学仍然未知。在我们的初步研究中， 将老鼠暴露在捕食者的气味压力下，并根据环境将受试者分为易感者和适应者。 在高架十字迷宫中的回避和高度焦虑行为。使用这种方法，我们发现， 易受伤害者而非易受伤害者，表现出自我施用可卡因的倾向增加。您因前述 确定了不同的多巴胺系统变化与易感表型相关。在 结合我们的初步研究，拟议的研究旨在首先确定净效应， 终末和体树突DA系统的改变，使用体内测量DA活性，其次， 通过检查DA终末或DA神经元索马，分离DA信号传导中净变化的来源 独立地。