Disruption to cortical dopamine systems following adolescent social stress

虽然哺乳动物的青春期是一个令人难以置信的形成期，但它也是一个对压力暴露的负面影响更容易受到影响的时期。特别是，成年后出现的认知缺陷被认为是压力导致前额叶皮层多巴胺系统中断的结果，该系统在青春期经历动态变化。对于许多青春期哺乳动物来说，一种常见的压力形式是社交攻击，但目前还不清楚这可能会如何影响皮质多巴胺系统，从而导致后来的认知功能障碍。这项研究将使用一只老鼠模型，通过检测青春期经历的社交攻击对各种已知的调节多巴胺活动的标记物的影响，来检验青少年皮质多巴胺系统特别容易受到社会压力的假设。然后，这些标志物的变化将与认知功能的负面变化相关，并辅以实验检验认知缺陷是否可以通过药物逆转。这些发现将提供新的信息，说明在青春期发生巨大变化的基本大脑系统如何受到社会环境因素的负面影响，从而导致长期的不适应行为表达，从而为调节青春期至成年期前额叶皮层多巴胺活动的机制的发展提供进一步的洞察。该项目将产生广泛的教育影响。南达科他州从大学前到研究生阶段的学生将有机会参与这些研究，为他们提供有意义和宝贵的研究经验，这是他们在科学事业中取得成功所必需的。调查人员还将自愿在地区高中、本科生和部落大学以及更大的社区中介绍和讨论这项工作。这将向更广泛的受众传播科学知识，突出青春期社会压力对相关群体的负面影响，并使这些群体接触到科学研究和教学的潜力，将其作为一种直接贡献社会的职业。

While mammalian adolescence is an incredibly formative time, it is also a period of increased susceptibility to the negative effects of stress exposure. In particular, cognitive deficits seen in adulthood are thought to result from stress-induced disruption of the prefrontal cortex dopamine system, which undergoes dynamic alterations during adolescence. For many adolescent mammals, a common form of stress is social aggression, but it is not known precisely how this may affect the cortical dopamine system to result in later cognitive dysfunction. This research will use a rat model to test the hypothesis that the adolescent cortical dopamine system is particularly vulnerable to social stress, by examining effects of social aggression experienced in adolescence on various markers known to regulate dopamine activity. Changes in these markers will then be related to negative alterations in cognitive function, with complimentary experiments examining whether cognitive deficits can be reversed pharmacologically. Findings will provide novel information about how an essential brain system that changes dramatically during adolescence can be negatively affected by socio-environmental factors to result in long term maladaptive behavioral expression, thus furnishing further insight into the development of mechanisms regulating prefrontal cortex dopamine activity across adolescence into adulthood. The project will have broad educational impact. South Dakotan students from pre-college to graduate level will have the opportunity to participate in these studies, providing them with meaningful and valuable research experiences as necessary for a successful career in science. The investigators will also volunteer to present and discuss this work at regional high schools, undergraduate and tribal colleges and the greater community. This will disseminate scientific knowledge to a wider audience, highlighting the negative impacts of social stress during adolescence to relevant groups, and exposing these groups to the potentials of scientific research and teaching as a vocation that directly contributes to society.