Cortisol effects on pupil size and locus coeruleus activity.

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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.