We primarily use zebrafish in our work. Zebrafish are a small freshwater teleost species that is widely used in biological sciences as a translational model. Zebrafish are extremely versatile, and have been used for many years in developmental biology and genetics. They are increasingly now coming to the forefront of neuroscience research, thanks to some fantastic work from influential groups arounds the world (eg see pioneering work on mapping neural circuits of behaviour from Misha Ahrens's group in the USA
We are interested in factors that affect why some drink alcohol at risky levels. For example, we know that stress is an important factor, but why some people are more sensitive to the effects of stress on relapse is not well understood. We think that personality is a critical factor, in particular, how impulsive or 'risk-taking' the person is. In a series of published studies, we have found that people show a greater increase in stress-induced craving for alcohol and drinking if they are high 'risk-takers'. This might help to explain individual differences in susceptibility to stress as a factor affecting risky drinking, and we are now working with colleagues at Queen Alexandra hospital in Portsmouth with patients attending hospital for alcohol-related health problems, to try to understand more about this process and ultimately, focus treatment more effectively.
Our ultimate goal is to understand the neural circuits underlying neuropsychiatric disorders, particularly those related to problems with impulse control, such as addiction and ADHD. There is a strong heritable (genetic) component to neuropsychiatric disorders, but the likelihood of developing the disorders is also affected by environmental challenges, such as stress. We exploit the range of benefits of using zebrafish as a model, including the genetic tools and recent improvements in zebrafish automated behavioural analysis. Adopting this approach allows us to characterise discrete components of neuropsychiatric disorders in terms of their underlying biology and help us to develop more effective treatments in the future. We have recently found that ADHD-linked gene (adgrl3.1) is linked to hyperactive and impulse control-deficits, and that this is under noradrenergic control (paper forthcoming). We currently have funded projects exploring ADHD, and drug addiction.
Animals held in captivity often display range of repetitive, morphologically invariant, habitual behavioural patterns, often referred to as stereotypies, or stereotypic behaviour. There are a few projects on stereotypic behaviour currently in the lab. We have previously worked extensively in large animal models, but recently we have become interested in the potential for exploiting the zebrafish to understand the neural basis of these behaviours, both in terms of their potential as indicators of poor welfare, but also in the sense that they may be very useful in helping us to understand habitual behaviours and compulsions in humans (e.g., addiction). Zebrafish show robust perseveration following pharmacological and stress-induced manipulations in the spontaneous y-maze task, and we are pursuing this as a model for spontaneous stereotypies.
Chronic exposure to alcohol, either during development or during adulthood, causes a range of physical and neurological problems. In the case of the developing foetus, there is the potential for Foetal Alcohol Spectrum Disorders (FASD). At the extreme end Foetal Alcohol Syndrome (FAS) causes significant physical and neurological disability. At the lower end, more subtle differences in behaviour result. Genetic differences in the foetus may be crucial in ameliorating or exacerbating the severity of the symptoms suffered as a result of exposure. We have been examining the effects of low/moderate alcohol exposure on zebrafish neurodevelopment and have published several papers in this area. In adult zebrafish, we have been testing the impact of chronic alcohol exposure on HPA axis and behavioural perturbations.