Brain nAChR Occupancy: Effect of Secondhand Smoke

Institution:	Brentwood Biomedical Research Institute
Investigator(s):	Arthur Brody, M.D.
Award Cycle:	2007 (Cycle 16)	Grant #: 16RT-0098	Award: $623,593
Subject Area:	Nicotine Dependence
Award Type:	Research Project Awards

Abstracts

Initial Award Abstract

Our research group (along with other research groups in the country) has developed a method to examine nicotine receptors (abbreviated as nAChRs in the title of this proposal) in the living human brain, using a type of brain imaging called "PET scanning." Studying nicotine receptors is important because these receptors are widespread throughout the brain, and because nicotine is widely regarded as the most important chemical in cigarettes that results in cigarette/tobacco addiction. The binding of nicotine to nicotine receptors in the brain is plays an important role in the pleasurable properties of cigarette smoking, as well as the effects of smoking on increasing attention and motivation. A recent study by our group (that was funded by the TRDRP) demonstrated that very small amounts of cigarette smoking result in 50% occupancy of nicotine receptors in the brain, while smoking a full cigarette or smoking as much as one wants results in saturation of these brain nicotine receptors. Research with secondhand smoke demonstrates that exposure to a smoky room (such as a smoky bar or restaurant) results in significant nicotine in the bloodstream. The nicotine levels found in the bloodstream of people exposed to secondhand smoke, along with the results of our study of cigarette smoking described above, indicate strongly that secondhand smoke exposure results in occupancy of nicotine receptors in the human brain. However, no one has yet demonstrated that secondhand smoke reaches the living human brain. For the study proposed here, we will examine the effects of secondhand smoke exposure on nicotine receptor occupancy in the brains of cigarette smokers and non-smokers, using PET scanning. Subjects will have a PET scan for 1 hour. They will then be exposed to secondhand smoke for 30 minutes, using a specially-designed smoke delivery system built for use with PET scanning. Some subjects will be exposed to high levels of secondhand smoke, while others will be exposed to lower levels, and still others will be exposed to no smoke (for comparison). All subjects will then be scanned for several more hours after the secondhand smoke exposure to examine changes in nicotine receptor occupancy from before to after the secondhand smoke exposure. To our knowledge, the study proposed here will be the first to demonstrate that secondhand smoke exposure reaches the living human brain and affects nicotine receptors. In smokers, secondhand smoke may diminish craving for cigarettes, and we will monitor this symptom throughout scanning to look for associations between craving and brain nicotine receptor occupancy. In non-smokers, secondhand smoke causes symptoms such as runny nose, coughing, watery eyes, headache, and chest tightness. These symptoms will be monitored throughout the PET scanning sessions, and we will determine whether or not these symptoms are related to the extent of nicotine receptor occupancy from secondhand smoke. Thus, in summary, the proposed study will determine the extent to which secondhand smoke exposure results in change in nicotine receptor occupancy in the brain. It will also determine whether these changes in nicotine receptor occupancy are associated with the symptoms people experience when they are exposed to secondhand smoke (such as cigarette craving reduction in smokers).

Publications

Brain nACHR occupancy: Effect of smoking a denicotinized cigarette.
Periodical: International Journal of Neuropsychopharmacology			Index Medicus:
Authors: Brody, AL, et al				ART
Yr: 2009	Vol: 12	Nbr:	Abs:	Pg: 305-316

Ventral striatal DA release in response to smoking.
Periodical: Neuropsychopharmacology			Index Medicus:
Authors: Brody, AL, et al				ART
Yr: 2009	Vol: 34	Nbr:	Abs:	Pg: 282-289

Smoking-Induced DA release in subjects with a history of major depressive disorder.
Periodical: Biological Psychiatry			Index Medicus:
Authors: Brody AL, et al				ART
Yr: 2009	Vol:	Nbr:	Abs:	Pg:

Effect of treatment for tobacco dependence on smoking-induced dopamine release
Periodical: Psychiatry Research Neuroimaging			Index Medicus:
Authors: Brody AL, et al				ART
Yr: 2009	Vol:	Nbr:	Abs:	Pg:

Brain nACHR occupancy: Effect of smoking a denicotinized cigarette.
Periodical: International Journal of Neuropsychopharmacology			Index Medicus:
Authors: Brody, AL, et al				ART
Yr: 2009	Vol: 12	Nbr:	Abs:	Pg: 305-316

Ventral striatal DA release in response to smoking.
Periodical: Neuropsychopharmacology			Index Medicus:
Authors: Brody, AL, et al				ART
Yr: 2009	Vol: 34	Nbr:	Abs:	Pg: 282-289

Smoking-Induced DA release in subjects with a history of major depressive disorder.
Periodical: Biological Psychiatry			Index Medicus:
Authors: Brody AL, et al				ART
Yr: 2009	Vol:	Nbr:	Abs:	Pg:

Effect of treatment for tobacco dependence on smoking-induced dopamine release
Periodical: Psychiatry Research Neuroimaging			Index Medicus:
Authors: Brody AL, et al				ART
Yr: 2009	Vol:	Nbr:	Abs:	Pg: