Effect of secondhand smoke on occupancy of nicotinic acetylcholine receptors in brain

Arthur L. Brody, Mark A. Mandelkern, Edythe D. London, Aliyah Khan, Daniel Kozman, Matthew R. Costello, Evan E. Vellios, Meena M. Archie, Rebecca Bascom, Alexey G. Mukhin

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Context: Despite progress in tobacco control, secondhand smoke (SHS) exposure remains prevalent worldwide and is implicated in the initiation and maintenance of cigarette smoking. Objective: To determine whether moderate SHS exposure results in brain α4β2* nicotinic acetylcholine receptor (nAChR) occupancy. Design, Setting, and Participants: Positron emission tomography scanning and the radiotracer 2-[18F]fluoro-3-(2(S) azetidinylmethoxy) pyridine (also known as 2-[18F]fluoro-A-85380, or 2-FA) were used to determine α4β2* nAChR occupancy from SHS exposure in 24 young adult participants (11 moderately dependent cigarette smokers and 13 nonsmokers). Participants underwent two bolus-plus-continuous-infusion 2-FA positron emission tomography scanning sessions during which they sat in the passenger's seat of a car for 1 hour and either were exposed to moderate SHS or had no SHS exposure. The study took place at an academic positron emission tomography center. Main Outcome Measure: Changes induced by SHS in 2-FA specific binding volume of distribution as ameasure of α4β2* nAChR occupancy.Results: An overall multivariate analysis of variance using specific binding volume of distribution values revealed a significant main effect of condition (SHS vs control) (F1,22=42.5, P<.001) but no between-group (smoker vs nonsmoker) effect. Exposure to SHS led to a mean 19% occupancy of brain α4β2* nAChRs (1-sample t test, 2-tailed, P<.001). Smokers had both a mean 23% increase in craving with SHS exposure and a correlation between thalamic α4β 2* nAChR occupancy and craving alleviation with subsequent cigarette smoking (Spearman ρ=-0.74, P=.01). Conclusions: Nicotine from SHS exposure results in substantial brain α4β2 * nAChR occupancy in smokers and nonsmokers. Study findings suggest that such exposure delivers a priming dose of nicotine to the brain that contributes to continued cigarette use in smokers. This study has implications for both biological research into the link between SHS exposure and cigarette use and public policy regarding the need to limit SHS exposure in cars and other enclosed spaces.

Original languageEnglish (US)
Pages (from-to)953-960
Number of pages8
JournalArchives of General Psychiatry
Volume68
Issue number9
DOIs
StatePublished - Sep 1 2011

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Tobacco Smoke Pollution
Nicotinic Receptors
Brain
Tobacco Products
Positron-Emission Tomography
Nicotine
Smoking
Public Policy
Tobacco
Young Adult
Analysis of Variance
Multivariate Analysis

All Science Journal Classification (ASJC) codes

  • Arts and Humanities (miscellaneous)
  • Psychiatry and Mental health

Cite this

Brody, A. L., Mandelkern, M. A., London, E. D., Khan, A., Kozman, D., Costello, M. R., ... Mukhin, A. G. (2011). Effect of secondhand smoke on occupancy of nicotinic acetylcholine receptors in brain. Archives of General Psychiatry, 68(9), 953-960. https://doi.org/10.1001/archgenpsychiatry.2011.51
Brody, Arthur L. ; Mandelkern, Mark A. ; London, Edythe D. ; Khan, Aliyah ; Kozman, Daniel ; Costello, Matthew R. ; Vellios, Evan E. ; Archie, Meena M. ; Bascom, Rebecca ; Mukhin, Alexey G. / Effect of secondhand smoke on occupancy of nicotinic acetylcholine receptors in brain. In: Archives of General Psychiatry. 2011 ; Vol. 68, No. 9. pp. 953-960.
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abstract = "Context: Despite progress in tobacco control, secondhand smoke (SHS) exposure remains prevalent worldwide and is implicated in the initiation and maintenance of cigarette smoking. Objective: To determine whether moderate SHS exposure results in brain α4β2* nicotinic acetylcholine receptor (nAChR) occupancy. Design, Setting, and Participants: Positron emission tomography scanning and the radiotracer 2-[18F]fluoro-3-(2(S) azetidinylmethoxy) pyridine (also known as 2-[18F]fluoro-A-85380, or 2-FA) were used to determine α4β2* nAChR occupancy from SHS exposure in 24 young adult participants (11 moderately dependent cigarette smokers and 13 nonsmokers). Participants underwent two bolus-plus-continuous-infusion 2-FA positron emission tomography scanning sessions during which they sat in the passenger's seat of a car for 1 hour and either were exposed to moderate SHS or had no SHS exposure. The study took place at an academic positron emission tomography center. Main Outcome Measure: Changes induced by SHS in 2-FA specific binding volume of distribution as ameasure of α4β2* nAChR occupancy.Results: An overall multivariate analysis of variance using specific binding volume of distribution values revealed a significant main effect of condition (SHS vs control) (F1,22=42.5, P<.001) but no between-group (smoker vs nonsmoker) effect. Exposure to SHS led to a mean 19{\%} occupancy of brain α4β2* nAChRs (1-sample t test, 2-tailed, P<.001). Smokers had both a mean 23{\%} increase in craving with SHS exposure and a correlation between thalamic α4β 2* nAChR occupancy and craving alleviation with subsequent cigarette smoking (Spearman ρ=-0.74, P=.01). Conclusions: Nicotine from SHS exposure results in substantial brain α4β2 * nAChR occupancy in smokers and nonsmokers. Study findings suggest that such exposure delivers a priming dose of nicotine to the brain that contributes to continued cigarette use in smokers. This study has implications for both biological research into the link between SHS exposure and cigarette use and public policy regarding the need to limit SHS exposure in cars and other enclosed spaces.",
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Brody, AL, Mandelkern, MA, London, ED, Khan, A, Kozman, D, Costello, MR, Vellios, EE, Archie, MM, Bascom, R & Mukhin, AG 2011, 'Effect of secondhand smoke on occupancy of nicotinic acetylcholine receptors in brain', Archives of General Psychiatry, vol. 68, no. 9, pp. 953-960. https://doi.org/10.1001/archgenpsychiatry.2011.51

Effect of secondhand smoke on occupancy of nicotinic acetylcholine receptors in brain. / Brody, Arthur L.; Mandelkern, Mark A.; London, Edythe D.; Khan, Aliyah; Kozman, Daniel; Costello, Matthew R.; Vellios, Evan E.; Archie, Meena M.; Bascom, Rebecca; Mukhin, Alexey G.

In: Archives of General Psychiatry, Vol. 68, No. 9, 01.09.2011, p. 953-960.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effect of secondhand smoke on occupancy of nicotinic acetylcholine receptors in brain

AU - Brody, Arthur L.

AU - Mandelkern, Mark A.

AU - London, Edythe D.

AU - Khan, Aliyah

AU - Kozman, Daniel

AU - Costello, Matthew R.

AU - Vellios, Evan E.

AU - Archie, Meena M.

AU - Bascom, Rebecca

AU - Mukhin, Alexey G.

PY - 2011/9/1

Y1 - 2011/9/1

N2 - Context: Despite progress in tobacco control, secondhand smoke (SHS) exposure remains prevalent worldwide and is implicated in the initiation and maintenance of cigarette smoking. Objective: To determine whether moderate SHS exposure results in brain α4β2* nicotinic acetylcholine receptor (nAChR) occupancy. Design, Setting, and Participants: Positron emission tomography scanning and the radiotracer 2-[18F]fluoro-3-(2(S) azetidinylmethoxy) pyridine (also known as 2-[18F]fluoro-A-85380, or 2-FA) were used to determine α4β2* nAChR occupancy from SHS exposure in 24 young adult participants (11 moderately dependent cigarette smokers and 13 nonsmokers). Participants underwent two bolus-plus-continuous-infusion 2-FA positron emission tomography scanning sessions during which they sat in the passenger's seat of a car for 1 hour and either were exposed to moderate SHS or had no SHS exposure. The study took place at an academic positron emission tomography center. Main Outcome Measure: Changes induced by SHS in 2-FA specific binding volume of distribution as ameasure of α4β2* nAChR occupancy.Results: An overall multivariate analysis of variance using specific binding volume of distribution values revealed a significant main effect of condition (SHS vs control) (F1,22=42.5, P<.001) but no between-group (smoker vs nonsmoker) effect. Exposure to SHS led to a mean 19% occupancy of brain α4β2* nAChRs (1-sample t test, 2-tailed, P<.001). Smokers had both a mean 23% increase in craving with SHS exposure and a correlation between thalamic α4β 2* nAChR occupancy and craving alleviation with subsequent cigarette smoking (Spearman ρ=-0.74, P=.01). Conclusions: Nicotine from SHS exposure results in substantial brain α4β2 * nAChR occupancy in smokers and nonsmokers. Study findings suggest that such exposure delivers a priming dose of nicotine to the brain that contributes to continued cigarette use in smokers. This study has implications for both biological research into the link between SHS exposure and cigarette use and public policy regarding the need to limit SHS exposure in cars and other enclosed spaces.

AB - Context: Despite progress in tobacco control, secondhand smoke (SHS) exposure remains prevalent worldwide and is implicated in the initiation and maintenance of cigarette smoking. Objective: To determine whether moderate SHS exposure results in brain α4β2* nicotinic acetylcholine receptor (nAChR) occupancy. Design, Setting, and Participants: Positron emission tomography scanning and the radiotracer 2-[18F]fluoro-3-(2(S) azetidinylmethoxy) pyridine (also known as 2-[18F]fluoro-A-85380, or 2-FA) were used to determine α4β2* nAChR occupancy from SHS exposure in 24 young adult participants (11 moderately dependent cigarette smokers and 13 nonsmokers). Participants underwent two bolus-plus-continuous-infusion 2-FA positron emission tomography scanning sessions during which they sat in the passenger's seat of a car for 1 hour and either were exposed to moderate SHS or had no SHS exposure. The study took place at an academic positron emission tomography center. Main Outcome Measure: Changes induced by SHS in 2-FA specific binding volume of distribution as ameasure of α4β2* nAChR occupancy.Results: An overall multivariate analysis of variance using specific binding volume of distribution values revealed a significant main effect of condition (SHS vs control) (F1,22=42.5, P<.001) but no between-group (smoker vs nonsmoker) effect. Exposure to SHS led to a mean 19% occupancy of brain α4β2* nAChRs (1-sample t test, 2-tailed, P<.001). Smokers had both a mean 23% increase in craving with SHS exposure and a correlation between thalamic α4β 2* nAChR occupancy and craving alleviation with subsequent cigarette smoking (Spearman ρ=-0.74, P=.01). Conclusions: Nicotine from SHS exposure results in substantial brain α4β2 * nAChR occupancy in smokers and nonsmokers. Study findings suggest that such exposure delivers a priming dose of nicotine to the brain that contributes to continued cigarette use in smokers. This study has implications for both biological research into the link between SHS exposure and cigarette use and public policy regarding the need to limit SHS exposure in cars and other enclosed spaces.

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