David Balfour

Although the proportion of the population who smoke tobacco has fallen from its peak in the middle of the last century, approximately 25% of Scottish people continue to smoke and smoking remains one of the principal avoidable causes of serious illness and premature death. It is widely accepted that a majority of habitual smokers are addicted to the nicotine present in tobacco smoke and that this is the reason that most smokers find it difficult to quit the habit successfully. My research has, for many years, explored the psychopharmacological properties of nicotine, especially those which may contribute to the role of nicotine in tobacco dependence. My work has focused on the role of monoamine systems in the behavioural response to nicotine, notably the role of the serotonergic projections to the hippocampus and the mesolimbic dopamine projections to the nucleus accumbens. These studies were the first to show that nicotine, when inhaled in tobacco smoke, evokes changes in the density of neuronal nicotinic receptors and serotonergic activity in human brain which are thought to play important roles in the development of tobacco addiction.

Other studies have used in vivo microdialysis to investigate the effects of repeated or chronic nicotine on dopamine overflow into the extracellular space of core and shell subdivisions of the nucleus accumbens and their role in the behavioural responses to chronic nicotine. These studies were the first to demonstrate that repeated nicotine administration results in sensitisation of its effects on DA overflow in the core subdivision of the accumbens. It now seems likely that this neural sensitisation may play an important role in the way that sensory cues, paired with the delivery of nicotine, exert their effects on behaviour. These cues are now thought to play a pivotal role in nicotine and tobacco dependence. Recent work in my laboratory suggests that the effects of nicotine on DA release in the accumbal shell may play an important role in contextual learning – that is the way in which the place where nicotine is taken elicits a craving for nicotine. Future studies will focus on the neural mechanisms which mediate contextually-conditioned responding for nicotine and the potential of targeting these systems in the treatment of tobacco dependence.

Obesity and its consequences, diabetes and cardiovascular disease, are important concerns for public health and increasing efforts are being directed at treating this problem. A recent research interest of the laboratory relates to the role of diet on behaviour. A primary aim of the experiments is explore the possibility that components of the diets themselves may impair the ability of the individual to change their dietary habits in manner similar, but not necessarily identical, to those of a drug of dependence. These studies, performed in collaboration with Caroline Stewart, Alison McNeilly and Calum Sutherland, have shown that diets rich in saturated fat rapidly exert effects on responding for a palatable food reward which may be characteristic of perseveration. These effects occur within two weeks of starting the diet and occur before the animals are frankly obese or diabetic. Future studies will explore the neural and behavioural mechanisms which underpin the effects and the extent to which they might be reversed using pharmacological or behavioural approaches.

I lecture on the neurobiology of drug dependence on courses to medical students and Honours Pharmacology students.