Cortisol effects on pupil size and locus coeruleus activity.

压力对认知、动机和行为都有很大的影响。这些变化的一个主要因素是下丘脑-垂体-肾上腺（HPA）轴在压力下的激活以及肾上腺释放的皮质醇对大脑回路的影响。我们已经找到证据证明下丘脑中轴和脑干一个叫做蓝斑核的去甲肾上腺素小核之间存在联系，蓝斑核在冷漠中被破坏，这是一种极度缺乏动力的状态。我们现在想在健康的人类志愿者中探索这种联系，使用瞳孔测量法，瞳孔大小的测量来调查蓝斑的活动。本项目将使用皮质醇和去甲肾上腺素受体拮抗剂对健康人类志愿者进行瞳孔测量奖励任务，以研究一种新的冷漠机制。具体目标包括：开展一项健康的人类志愿者研究，实施药物治疗以阻断皮质醇和去甲肾上腺素信号，同时在奖励任务中实施瞳孔测量技术。这是一个多学科项目，成功的申请人将与心理学和分子内分泌学的科学家团队合作。

Stress has powerful effects on cognition, motivation and behaviour. A major factor for these changes is the activation of the hypothalamic-pituitary-adrenal (HPA) axis by stress and the effects of the cortisol released by the adrenal gland on brain circuits. We have found evidence for a connection between the HPA axis, and a small brainstem norepinephrine nucleus called the locus coeruleus that becomes disrupted in apathy, a profound lack of motivation. We now want to explore this connection in healthy human volunteers using pupillometry, the measure of pupil size to investigate locus coeruleus activity. This project will administer cortisol and norepinephrine receptor antagonists on healthy human volunteers undergoing a reward task with pupillometry to investigate a novel mechanism of apathy. Specific objectives include: - Developing a pupillometric technique to investigate locus coeruleus activity - Designing a reward task to measure extrinsic motivation Carrying out a healthy human volunteers study, administering drug treatments to block cortisol and norepinephrine signalling whilst implementing the pupillometric technique with the reward task This is a multidisciplinary project, and the successful applicant will work with a team of scientists in psychology and molecular endocrinology.