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Bupropion and nicotine dependence: behavior & neurochemisty

Institution: Scripps Research Institute
Investigator(s): Neil Paterson, B.Sc., MBCh.B.
Award Cycle: 2005 (Cycle 14) Grant #: 14FT-0056 Award: $37,500
Subject Area: Nicotine Dependence
Award Type: Postdoctoral Fellowship Awards
Abstracts

Initial Award Abstract
Tobacco smoking, which is attributed primarily to the addictive properties of nicotine contained in tobacco smoke, continues to be a global health problem. Tobacco smoking leads to over four hundred thousand deaths per year in the USA alone. The cost to society is significant in terms of health problems that frequently lead to death, associated medical costs and human suffering. It has been projected that by the year 2020 tobacco will become the largest single health problem worldwide, leading to approximately 8.4 million deaths annually. A study sponsored by the World Health Organization and the World Bank estimates that in high-income countries smoking-related healthcare expenses account for 6-15% of all annual healthcare costs. Considering that the risk for developing diseases associated with tobacco smoking is reduced when smoking is stopped, there is great incentive to conduct high quality biomedical research to develop more effective prevention and cessation strategies for tobacco smoking than currently available treatments and strategies. The present fellowship addresses the large societal and medical problem of tobacco smoking by conducting biomedical research that will help us better understand the necessary attributes of bupropion, the most effective pharmacological treatment for smoking cessation currently available. The knowledge generated by the planned research will greatly assist in the development of new innovative treatments to assist people to abstain from smoking and remain abstinent. Currently available smoking cessation therapies are not particularly effective, as shown by the high failure rates of smoking cessation attempts. Thus, it is important to invest research resources in understanding the salient features of the most effective smoking medication currently available, to assist in the design and development of more effective future pharmacotherapies. The main reasons for the difficulty in initiating and maintaining abstinence from tobacco smoking may be either the aversive nicotine withdrawal syndrome or the positive ‘euphoric’ effects of smoking a cigarette. The present studies will resolve this question by determining how bupropion affects these two components of nicotine addiction. In the brain, nicotine produces its effects by increasing dopamine levels in specific brain areas, via activation of nicotine receptors. Dopamine is one of several neurotransmitters found in the brain; others include norepinephrine. Bupropion has several different effects on dopamine, norepinephrine and nicotine receptors. Proposed studies will explore which of bupropion’s various effects are most important in decreasing nicotine intake and attenuating the nicotine withdrawal syndrome. Nicotine withdrawal is associated with low levels of dopamine due to the absence of nicotine. It may also be associated with alterations in norepinephrine levels. Additional proposed studies will explore how bupropion affects dopamine and norepinephrine signalling during nicotine withdrawal. Thus, the proposed research will determine how bupropion aids smoking cessation and which of bupropion’s various pharmacological effects are most important in smoking cessation. In summary, the planned studies will provide us with crucial information that will help us design more effective pharmacological treatments to help people quit smoking, and thus avoid the detrimental effects of tobacco smoking on health.
Publications

Chronic bupropion attenuated nicotine withdrawal via inhibition of dopamine reuptake in the nucleus accumbens shell.
Periodical: European Journal of Neuroscience Index Medicus:
Authors: Neil Paterson ART
Yr: 2007 Vol: 25 Nbr: 10 Abs: Pg: 3099-3108

Chronic but not acute, desipramine attenuated nicotine withdrawal and secreased nicotine self administration in the rat.
Periodical: Biological Psychiatry Index Medicus:
Authors: Neil Paterson ABS
Yr: 2007 Vol: Nbr: Abs: Pg:

Chronic but not acute, desipramine treatment prevented nicotine withdrawal and decreased nicotine self administration in rats.
Periodical: Biological Psychiatry Index Medicus:
Authors: Neil Paterson ABS
Yr: 2007 Vol: Nbr: Abs: Pg: