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Perspectives on tobacco dependence: The biology of nicotine addiction
Susan Wonnacott, Professor of Neuroscience, Department of Biology and Biochemistry, University of Bath, UK
Abstract
For many years the addiction liability of nicotine was disputed. Demonstration that laboratory animals readily display nicotine-seeking behaviour in behavioural tests and exhibit a quantifiable physical withdrawal syndrome when denied nicotine has established that nicotine is dependence producing. After a brief synopsis of this background, this talk will focus on how nicotine acts on the brain to achieve dependence.
The molecular target for nicotine is the family of nicotinic acetylcholine receptors (nAChRs). Physiologically these receptors respond to the natural transmitter acetylcholine. Nicotine can also activate them but, unlike acetylcholine, nicotine remains for much longer and as a consequence a proportion of nAChRs are desensitised or switched off. Repeated or chronic exposure to nicotine leads to an increase in the number of nAChRs in the brains of laboratory animals and human smokers. The activation of nAChRs by nicotine can have a number of consequences in the recipient nerve cells, including the release of various other neurotransmitters. The one that has received most attention in the context of addiction is dopamine, released from the so-called ‘reward pathway’: targeting these nAChRs provides the rationale for the efficacy of varenicline (Champix) for smoking cessation. Initially dopamine release may be triggered by novelty and interpreted as ‘liking’ the stimulus. But repeated intake of nicotine and activation of nAChRs results in a switch that gives rise to ‘craving’ and drug-seeking behaviour. The permanence of this change contributes to the prevalence of relapse among ex-smokers.
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About the presenter
Sue Wonnacott is Professor of Neuroscience at the Department
of Biology and Biochemistry in the University of Bath since 2000. Her research interests focus on the molecular and cellular actions of nicotine and nicotinic receptors (nAChRs) in the mammalian brain. Research related to nicotine addiction includes (1) an exploration of the nAChRs that influence release of the ‘reward’ transmitter dopamine in the brain; (2) changes in response to chronic nicotine treatment, in vivo and in cell culture; (3) the effects of smoking cessation drugs, notably bupropion (Zyban); (4) a vaccination strategy targeting cotinine. A member of SRNT and contributor to Nicotine Addiction in Britain, RCP, 2000.
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