Therapeutic potential of neurosteroids in the treatment of anxiety and social avoidance

Neurosteroids are naturally occurring steroid compounds produced by the brain in response to stressful events, and they may serve a protective function by reducing the adverse consequences of stress, such as maladaptive increases in avoidance behaviour and anxiety that interfere with daily life. Neurosteroids can reduce the excitability of neurons by enhancing the activation of GABAA receptors—the most common mediators of inhibitory neurotransmission in the brain. Reduced basal and / or stress-induced levels of neurosteroids may be a risk factor for the development of psychiatric disorders such as anxiety, depression, and PTSD. Appropriately timed neurosteroid supplementation may reverse or prevent the adverse effects of reduced neurosteroid levels. The current project would focus on the potential role of neurosteroids in limiting the increases in anxiety and social avoidance caused by acute and / or chronic stress in mice. Some situations present the possibility of both rewarding or aversive outcomes, and a decision on the optimal course of action—i.e. to approach or avoid a stimulus—must be made. Situations that reflect this conflict include social interaction, during which the desire to interact socially is constrained by the possibility of aversive or aggressive interactions, and exploration-based tasks in which the natural desire of a rodent to explore is constrained by its fear of brightly lit open spaces. In anxiety disorders, the approach / avoidance balance may be maladaptively shifted towards avoidance. The goal of the current project will be to determine whether the administration of neurosteroids can reverse a stress-induced increase in avoidance behaviour, and, in parallel experiments, to investigate the effects of stress and neurosteroid administration on task-related neuronal activity in the hippocampus. This will provide information about the links between neuronal activity and approach-avoidance conflict, and the ways in which neurosteroid administration can shift the balance away from avoidance towards goal-directed action.

The student undertaking this project will be part of the School of Medicine ‘Neuro Group’ located in the MSI Building on the University of Dundee’s City Campus. You will have access to well-equipped laboratories and the opportunity to learn from staff and other students in a supportive environment. Training in all relevant techniques will be provided.

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Our research community thrives on the diversity of students and staff which helps to make the University of Dundee a UK university of choice for postgraduate research. We welcome applications from all talented individuals and are committed to widening access to those who have the ability and potential to benefit from higher education.