Professor David JK Balfour

Emeritus Professor of Behavioural Pharmacology

Address:

Division of Neuroscience
Mailbox 6, Level 6
Ninewells Hospital & Medical School
Dundee, DD1 9SY

Phone Number:

+(44) 01382 383168

Email Address:

d.j.k.balfour@dundee.ac.uk

Biography

Professor Balfour graduated with a BSc (1968) and PhD (1971) in biochemistry from St Andrews University. He then worked as a research scientist in the pharmacology department of the Tobacco Research Council Laboratories (1971-1973) before moving to the Chemical Defence Establishment, Porton Down. He was appointed to the Pharmacology Department at Dundee University in 1976 and was appointed Professor of Behavioural Pharmacology in 2000. His work in Dundee has focused primarily of the psychopharmacological properties of nicotine, especially those effects which may be implicated in the development of addiction to tobacco. He was awarded a DSc (St Andrews University) for a thesis based on these studies in 2013.

He was a founding member of the Society for Research on Nicotine and Tobacco. He was elected President of the Society in 2005, the first non-American to be elected to this post. He was awarded the Langley Award by the Society in 2009. This prize is awarded for internationally recognised ground-breaking basic research in the field of nicotine pharmacology. Professor Balfour has served on the editorial boards of several journal related to pharmacology and addiction and am currently the Editor-in-Chief of Nicotine & Tobacco Research.

Research

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.

Publications

Maguire EP, Mitchell EA, Greig S, Corteen N, Balfour DJK, Swinny JD, Lambert JJ, Belelli D (2014) Extrasynaptic glycine receptors of rodent dorsal raphe serotonergic neurons: a sensitive target for ethanol. Neuropsychopharmacology, in press.

Gradin VB, Baldacchino A, Balfour D, Matthews K, Steele JD (2014) Abnormal Brain Activity during a Reward and Loss Task in Opiate Dependent Patients receiving Methadone Maintenance Therapy, Neuropsychopharmacology, in press.

Baldacchino A, Balfour DJK, Passett F, Humphris G, Matthews K (2012) Neuropsychological consequences of chronic opioid use: a quantitative review and meta-analysis. Neurosci Biobehav Rev, 36: 2056-2068.

Dani JA, Balfour DJK (2011) Historical and current scientific progress underlying nicotine addiction and tobacco use. Trends in Neurosci, 34: 363-392.

Tronci V, Balfour DJK (2011) The effects of the mGluR5 receptor antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP) on the stimulation of dopamine release evoked by nicotine in the rat brain.  Behav Brain Res, 219: 354-357.

Tronci V, Vronskaya S, Montgomery N, Mura D, Balfour DJK (2010) The effects of the mGluR5 receptor antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP) on behavioural responses to nicotine. Psychopharmacology, 211: 33-42.

Herd M B, Foister N, Chandra D, Peden D R, Homanics GE, Brown VJ, Balfour DJK, Lambert JJ, Belelli D (2009) Inhibition of thalamic excitability by THIP: a selective role for δ-GABAA receptors. Eur J Neurosci, 29: 177-187.

Balfour DJ (2009) Neuronal pathways mediating the behavioural and addictive properties of nicotine. Handb Exp Pharmacol, 192: 209-233.

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.

Sayer R, Robertson D, Balfour DJK, Breen KC, Stewart CA (2008) The effect of stress on the expression of the amyloid precursor on protein in rat brain. Neurosci Lett, 431: 197-200.

Paterson 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.

Paterson 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.

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

Scerri C, Stewart CA, Breen KC, Balfour DJK (2006) The effects of chronic nicotine on spatial learning and bromodeoxyuridine incorporation into the dentate gyrus of the rat. Psychopharmacology, 184: 540-546.

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.

Robertson DAF, Beattie JE, Reid IC, Balfour DJK (2005) Regulation of corticosteroid receptors in the rat brain: the role of serotonin and stress. Eur J Neurosci, 21: 1511-1520.

Teaching

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

PhD Supervision

2009 – 2013 Scott Greig (Full-time PhD) Research Topic:  The regulation of dorsal raphe 5-HT neurones by glycine (Supervised jointly with Prof Verity Brown, St Andrews University, Prof Jeremy Lambert & Dr Delia Belelli)

2008 – 2012 Dr Alex Baldacchino Research Topic: The effects of opiates on measures of psychological performance (Supervised jointly with Professor Keith Matthews)

2006 – 2009 Sara Johnson Research Topic: The effects of glucocorticoid hormones on APP processing in the rat brain (Supervised jointly with Dr Caroline Stewart)

2006 – 2008 Nicola Foister Research Topic: (Supervised jointly with Prof Verity Brown, St Andrews University, Prof Jeremy Lambert & Dr Delia Belelli, Dundee University)

2003 – 2006 Dr N. Paterson Research topic:  The neurobiology underlying nicotine withdrawal (Supervised jointly with Dr Athina Markou, The Scripps Institute, California)

2002 – 2005 C. Scerri Research topic:  The effects of nicotine on APP and Tau release and processing in the rat brain (Supervised jointly with Dr Kieran Breen)

2000 – 2004 R. Sayer Research topic:  The effects of stress on acetylcholinesterase in rat brain (Supervised jointly with Dr Kieran Breen & Dr Caroline Stewart)

1997 – 2000 A. Wright Research topic:  Interactions between ethanol and nicotine: a focus on the pathways implicated in dependence and J. Storey Research topic:  Hippocampal 5-HT projections as a target for antidepressant drugs

1996 – 1999 Dr R.X. Petrie Research topic:  Synaptic plasticity in animal models of affective disorder (Supervised jointly with Professor I.C. Reid)

1992 – 1996 C.E. Birrell Research topic:  The neurochemical mechanisms underlying sensitisation of the mesolimbic dopamine response to nicotine

1991 – 1995 J. Grant Research topic:  Studies on the mechanisms which mediate the psychopharmacological responses to angiotensin converting enzyme (ACE) inhibitors

1991 – 1995 F. Grant Research topic: The effects of selective neurokinin receptor ligands on the activity of serotonergic cells in the dorsal and median raphe of the rat brain

1985-1989 C.A. Graham Thesis:  Effects of nicotine on behavioural and biochemical responses to stress

1985 – 1991 G.J.B. Winch Thesis:  An in vitro study of factors influencing the binding of tobacco alkaloids and nicotine metabolites to the central nicotinic receptor

1985 – 1990 J.L.W. Yau Thesis:  Some aspects of the in vitro modulation of the GABAA receptor by depressant barbiturates and pregnane steroids (Supervised jointly with Professor I.H. Stevenson)

1982 – 1985 A.M. Copland Thesis:  The role of hippocampal 5-hydroxytryptamine in the effects of diazepam on responses to aversive stimuli

1981 – 1984 T.T. Iyaniwura Thesis: An investigation of the effects of d-amphetamine on rat brain 5-hydroxytryptamine

1977 – 1980 N. Murray Thesis: Studies on the disposition and actions of lithium(supervised jointly with Dr D.S. Hewick)

1976 – 1981 M.E.M. Benwell Thesis: A study of a possible biochemical mechanism to account for nicotine dependence

Conferences

“Complementary Roles for the Accumbal Shell and Core in Nicotine Dependence” presented as part of a Novartis Foundation Symposium on Understanding Nicotine and Tobacco Addiction, Novartis Foundation, London May 2005.

“Nicotine addiction in animals: mechanisms and models” presented as part of a European Respiratory Society Symposium on Harm Reduction, Feney-Voltaire, France, October 2005

“Neurochemistry of nicotine addiction” to be presented as part of a symposium on The Neuropharmacology and Genetics of Nicotine Addiction, British Association of Psychopharmacology Annual Meeting, Oxford, July 2006

“Rethinking the dopamine hypothesis of nicotine addiction”. Plenary Lecture, Annual Meeting of SRNT Europe, Kusadasi, Turkey, September 2006

“Nicotine as a reinforcer: a psychobiological perspective”. Presented as part of a symposium on Non-Nicotinic Mechanisms of Tobacco Dependence. Annual Meeting of SRNT Europe, Kusadasi, Turkey, September 2006

“The addictive potential of nicotine”. Presented as part of symposium on “Targeting Smokers by Reduction: The Snus Connection Revisited”, European Respiratory Society Annual Conference, Stockholm, September 2007.

“The neurobiology of nicotine dependence” Presented as part of a symposium on “The Treatment of Tobacco Dependence”. Seoul February 2008

“Nicotine dependence”. Presented as part of a symposium on “Advances in the Treatment of Tobacco Dependence”. European Respiratory Society, Leuven, March 2008

“Is there more to dependence than just nicotine”. Presented in a symposium on "The tobacco epidemic? Prevention and treatment of the single largest threat to human health in the 21st century" as part the Bicentennary Meeting of the Swedish Medical Society, Stockholm April 2008.

Do Studies with Animals Tell Us Anything Useful About Tobacco Dependence? Plenary lecture at the Annual Meeting of the Society for Research on Nicotine and Tobacco, Dublin March 2009

“What Can Studies with Rodents Tell Us About Treatments for Tobacco Dependence” Symposium on Nicotine and Alcohol Dependence at the European Biomedical Research Association Conference, Helsinki June 2009.