We are interested in factors that affect why some people relapse following quitting alcohol. 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 preliminary work, we have found that non-addicted healthy drinkers show a greater increase in stress-induced craving for alcohol if they are high 'risk-takers'. This might help to explain individual differences in susceptibility to stress when trying to quit drinking, and we are now working with colleagues at Queen Alexandra hospital in Portsmouth with patients with a history of alcohol misuse, 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 disorder. 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 currently have projects exploring the neural basis of ADHD, and neural circuits of 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.
Prenatal exposure to alcohol causes a range of physical and neurological disabilities, collectively referred to as 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. For example, monozygotic twins (who share 100% of their genes and environment) that are exposed to alcohol during their mother's pregnancy are both affected 100% of the time; however, dizygotic twins (who share environment but 50% of their genes) are only both affected 63% of the time. Animal studies have been critical in increasing our understanding of this mechanism. We have been examining the effects of low/moderate alcohol exposure on zebrafish neurodevelopment.