Prof David Balfour

Research

Although the prevalence of smoking has been falling in recent years, tobacco smoking remains one of the major preventable causes of premature death, especially in Scotland. The research programme in my laboratory focuses on the neurobiological mechanisms underlying the addiction to tobacco and its treatment. It is widely accepted that nicotine is principal addictive component of tobacco and that a majority of habitual smokers find it very difficult to quit smoking because they have become addicted to the nicotine present in the smoke. As result, nicotine replacement therapy (NRT) has been used for many years as an aid to smoking cessation. The use of NRT improves cessation rates significantly, although the degree of success is disappointingly low. My group have characterised a number of the changes in specific regions of the brain of experimental animals and human smokers, particularly the prefrontal cortex, nucleus accumbens and hippocampus, which occur as result of chronic exposure to nicotine. Our current studies are seeking to determine the role of these changes in the neurobiology of nicotine dependence and to explore how an improved understanding of these mechanisms might contribute to the development of more successful aids to smoking cessation. There is evidence that the addictive properties of nicotine are enhanced by co-presentation with other components of tobacco smoke, especially those elements of the smoke which evoke sensory stimulation in the mouth, throat and bronchi. One of our current projects is exploring the extent to which specific neural responses to nicotine in the brain interact with stimuli of this type. There is also evidence that psychiatric co-morbidity, especially schizophrenia and depression, can greatly enhance the addictive potential of nicotine, many of the patients with these conditions becoming highly dependent upon tobacco. A second project in the laboratory focuses on the hypothesis that neurobiology underlying depression makes these smokers particularly vulnerable to the rewarding properties of nicotine. In this project we have already shown that exposure to depressogenic stimuli evokes changes the release of the neurotransmitter, serotonin, in the hippocampus, as system which also responds to chronic nicotine. Our working hypothesis proposes that this anatomic structure may play an important role in nicotine dependence in depressed individuals.

In collaboration with other members of staff, studies in my laboratory also explore the neurobiology underlying Alzheimer’s disease, current studies focusing on the potential role of type 2 diabetes as a vulnerability factor for the condition. Another area of research employ transgenic methodologies to investigate the putative role of specific receptors for the neurotransmitter, GABA, in anxiety and cognition. These studies are aimed at a better understanding the neurobiology underlying anxiety and conditions, such as Alzheimer’s disease and schizophrenia, in which impaired cognition plays an important role.

Recent publications

Storey JD, Robertson DAF, Beattie JE, Reid IC, Mitchell SN, Balfour DJK (2006) Behavioural and neurochemical responses evoked by repeated exposure to an elevated open platform. Behav Brain Res, 166: 220-229.

Fagerstom KO, Balfour DJK (2006) Neuropharmacology and potential efficacy of new treatments for tobacco dependence. Expert Opin. Investig Drugs, 15, 107-116.

Matta SG, Balfour DJ, Benowitz NL, Boyd RT, Buccafusco JJ, Caggiula AR, Craig CR, Collins AC, Damaj MI, Donny EC, Gardiner PS, Grady SR, Heberlein U, Leonard SS, Levin ED, Lukas RJ, Markou A, Marks MJ, McCallum SE, Parameswaran N, Perkins KA, Picciotto MR, Quik M, Rose JE, Rothenfluh A, Schafer WR, Stolerman IP, Tyndale RF, Wehner JM, Zirger JM (2006) Guidelines on Nicotine Dose Selection for In Vivo Research. Psychopharmacology, 190: 269-319.

Patterson NE, Balfour DJ, Markou A (2007) Chronic bupropion attenuates the anhedonic component of nicotine withdrawal in rats via inhibition of dopamine reuptake in the nucleus accumbens shell. Eur J Neurosci, 25: 3099-3108.

Patterson NE, Balfour DJ, Markou A (2008) Chronic bupropion differentially alters the reinforcing, reward-enhancing and conditioned motivational properties of nicotine in rats. Nic Tob Res, 10: 995-1008.

Robertson DAF, Beattie JE, Reid IC, Balfour DJK (2008) The Influence of 5, 7-dihydroxytryptamine lesions of the rat fornix-fimbria and cingulum bundles on spontaneous activity in an aversive maze. J Psychopharmacol, 22: 285-289.

Funding

Society for Endocrinology