Divergent Dopamine System Adaptions After Stress

摘要 压力会引发行为的病理变化，似乎会增加药物滥用的脆弱性。 尽管如此，只有一部分经历过类似压力事件的人会发展出明显的 因此，个体可能在应激后表现出敏感或有弹性的表型。近期 有证据表明，压力后的易感性和韧性与不同的适应能力有关 中脑边缘多巴胺系统，众所周知，它参与了物质使用的发展 无序。物质使用脆弱性的增加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不清楚。对于我们的初步研究，我们 将老鼠暴露在捕食者气味压力下，并根据环境将受试者区分为易感或有弹性 高架+迷宫中的回避和高度焦虑行为。使用这种方法，我们发现 易受影响的人，但不是有弹性的人，表现出自我给药的倾向增加。此外，我们还拥有 发现明显的多巴胺系统变化与易感表型有关。在……里面 与我们的初步研究相结合，拟议的研究旨在首先确定 用体内DA活性测量的终末和躯体树突状DA系统的改变，第二次到 通过检查DA终末或DA神经元胞体来分离DA信号净变化的来源 独立的。

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.