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Neuroadaptations underlying nicotine dependence

Institution: Scripps Research Institute
Investigator(s): Adrie Bruijnzeel, Ph.D.
Award Cycle: 2002 (Cycle 11) Grant #: 11FT-0112 Award: $60,379
Subject Area: Nicotine Dependence
Award Type: Postdoctoral Fellowship Awards
Abstracts

Initial Award Abstract
More than 10 years ago the United States Surgeon General recognized tobacco-smoking as the number one preventable cause of death in the USA (US Department of Health and Human Services 1988). In the same report, it was also indicated that nicotine is the main component of cigarettes that leads to the habit of smoking because the individual gradually becomes addicted to nicotine. The fact that nicotine is addictive is indicated by the fact that smokers frequently fail to quit. Approximately 80% of the individuals attempting to quit resume smoking within a year, even though these individuals are often fully aware of the potential harmful effects of smoking on health. One of the reasons that quitting smoking is difficult is that it results in a withdrawal syndrome consisting of both affective (e.g., anxiety, irritability) and somatic components (e.g., gastrointestinal disorders, weight gain). Increasing evidence, however, suggests that the affective symptoms are of greater importance in contributing to relapse than the somatic symptoms.

In the brain, nicotine produces its effects by activating specific sites called receptors, and more specifically, nicotinic acetylcholine receptors. Stimulation of the nicotinic acetylcholine receptors induces a variety of secondary effects involving the neurotransmitter dopamine that acts on dopamine receptors. There is evidence that adaptations in the brain cholinergic and dopaminergic system resulting from long-term nicotine exposure are responsible for the withdrawal signs experienced after quitting smoking. Hence, the aim of the proposed studies is to investigate which parts of the brain reward circuit and which receptor subtypes are responsible for the affective symptoms of nicotine withdrawal. It is predicted that the receptor blockers will induce an elevation in brain reward thresholds in the nicotine dependent, but not in the non-dependent subjects. This pattern of results will indicate that adaptations in the acetylcholine and dopamine receptors in the selected subregions of the brain reward circuit are critically involved in the development of nicotine dependence.

The proposed studies will provide valuable information that could help in the design of effective pharmacological treatments for smoking cessation, and the avoidance of the detrimental effects of tobacco smoking on health.
Publications

Characterization of the effects of bupropion on the reinforcing properties of nicotine and food in rats.
Periodical: Synapse Index Medicus:
Authors: Bruijnzeel AW, Markou A ART
Yr: 2003 Vol: 50 Nbr: Abs: Pg: 20-28

Bupropion enhances brain reward function and reverses the affective and somatic aspects of nicotine withdrawal in the rat.
Periodical: Psychopharmacology Index Medicus:
Authors: Cryan JF< Bruijnzeel AW, Skjei KL, Markou A ART
Yr: 2003 Vol: 168 Nbr: Abs: Pg: 347-358

The antidepressant bupropion enhances brain reward function and reverses nicotine withdrawal in the rat.
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Cryan JF< Bruijnzeel AW, Skjei KL, Markou A ABS
Yr: 0 Vol: Nbr: Abs: Pg:

The antidepressant bupropion enhances brain reward function and reverses nicotine withdrawal in the rat.
Periodical: TRDRP Annual Report to the State of California Legislature Index Medicus:
Authors: Bruinjzeel AW ABS
Yr: 2002 Vol: Nbr: Abs: Pg:

Increased sensitivity to the nicotinic receptor antagonist dihydro-beta-erythroidine injected into the ventral tegmental area of rats chronically exposed to nicotine.
Periodical: European Behavioural Pharmacology Society Index Medicus:
Authors: Bruijnzeel AW, Markou A ABS
Yr: 2003 Vol: Nbr: Abs: Pg:

Characterization of the effects of bupropion on the reinforcing and incentive-motivational properties of nicotine and food in rats.
Periodical: College on Problems of Drug Dependence Index Medicus:
Authors: Bruijnzeel AW, Markou A ABS
Yr: 0 Vol: Nbr: Abs: Pg: