Temporal Change in Human Nicotinic Acetylcholine Receptor After Smoking Cessation: 5IA SPECT Study

Abstract

Nicotinic acetylcholine receptors (nAChRs) are of great interest because they are implicated in various brain functions. They also are thought to play an important role in nicotine addiction of smokers. Chronic (2)-nicotine, a nAChR agonist, treatment in mice and rats elicits a dose-dependent increase in nAChRs in the brain. Upregulation of nAChRs in postmortem human brains of smokers has also been reported. However, changes in nAChRs after cigarette smoking cessation in humans are poorly understood. The aim of this study was to detect the dynamic changes of nAChRs after smoking and smoking cessation in the brains of living subjects. Methods: We performed 5-123 Iiodo-A-85380 ( 123 I-5IA) SPECT on nonsmokers and smokers (n 5 16) who had quit smoking for 4 h, 10 d, and 21 d and calculated and compared distribution volumes (Vt) of 123 I-5IA. Results: The binding potential of nAChRs (Vt of 123 I-5IA) in the brains of smokers decreased by 33.5% 6 10.5% after 4 h of smoking cessation, increased by 25.7% 6 9.2% after 10 d of smoking cessation, and decreased to the level of nonsmokers after 21 d of smoking cessation. Conclusion: Because the upregulation of the nAChRs of the smokers after chronic exposure of the nicotine was downregulated to the nonsmokers' level by around 21 d after smoking cessation, the upregulation is a temporary effect. The decrease in nicotinic receptors to nonsmoker levels may be the breaking point during the nicotine withdrawal period.

Greater Nicotinic Acetylcholine Receptor Density in Smokers Than in Nonsmokers: A PET Study with 2-18F-FA-85380

“…In addition, the SPM analysis revealed that no brain region exhibited the opposite condition (i.e., V T /f P in nonsmoker > V T /f P in smoker). These observations were consistent with several reports of greater receptor densities in smokers than in nonsmokers in studies of postmortem tissue (5,6) and results from in vivo studies (28–30). We observed the greatest differences in V T /f P in the cerebellum and midbrain, with frontal cortex and pons also showing differences.…”

Greater Nicotinic Acetylcholine Receptor Density in Smokers Than in Nonsmokers: A PET Study with 2-18F-FA-85380

“…In addition, the SPM analysis revealed that no brain region exhibited the opposite condition (i.e., V T /f P in nonsmoker > V T /f P in smoker). These observations were consistent with several reports of greater receptor densities in smokers than in nonsmokers in studies of postmortem tissue (5,6) and results from in vivo studies (28–30). We observed the greatest differences in V T /f P in the cerebellum and midbrain, with frontal cortex and pons also showing differences.…”

β2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking

“…Additionally, they reported significantly lower β 2 *-nAChR availability at 21 days of abstinence compared to 10 days of abstinence. One difference is that the previous study18 had significantly lower β 2 *-nAChR availability in all regions at 4 hr of abstinence compared to the nonsmokers, while the current study reports lower thalamic but similar β 2 *-nAChR availability in the striatum, cerebellum and throughout the cortex compared to the nonsmoker group at 1 day of abstinence. This is interesting and likely due to high levels of residual nicotine or metabolites present in the brain at 4 hr of abstinence (versus ∼24 hours in the current study) resulting in lower β 2 *-nAChR availability.…”

“…This study is also consistent with a previous study18 demonstrating that higher β 2 *-nAChR availability in recently abstinent tobacco smokers compared to nonsmokers is temporary. In the previous study in men, β 2 *-nAChR availability decreased to nonsmoker levels in some subjects by 21 days of abstinence.…”

“…This may be because of the older average age (approximately 5 years) of participants in the current study, because ␤ 2 *-nAChR availability has been shown to decrease with age in nonsmokers. 77 This study and previous in vivo positron emission tomography 78 and SPECT 8,18 studies report no upregulation of thalamic ␤ 2 *-nAChR availability during acute abstinence, which conflicts with the findings of postmortem 2 and animal 8,79 studies. In general, this may be because of differences in methods or the higher relative dose of nicotine in the postmortem and animal studies.…”

Treatment for Tobacco Dependence: Effect on Brain Nicotinic Acetylcholine Receptor Density

“…No associations between a 4 b 2 * nAChR densities and treatment type were found, but significant associations were discovered between the extent of a 4 b 2 * nAChR density reduction and the amount of decreased cigarette usage. These results indicate that a 4 b 2 * nAChR density is strongly linked to the number of cigarettes smoked per day, but not to the treatment type being administered, and are consistent with our previous study of untreated smokers (Brody et al, 2013) and other studies linking nicotine (Marks et al, 2011;Yates et al, 1995;Zhang et al, 2002) and cigarette smoke (Mamede et al, 2007;Mukhin et al, 2008;Staley et al, 2006;Wullner et al, 2008) exposure with upregulation of a 4 b 2 * nAChRs in brain regions other than the thalamus. Because education about the biological effects of smoking and quitting smoking are standard parts of smoking-cessation psychotherapy (Fiore et al, 2008), the additional information found here could prove useful in treatment of smokers by letting them know that brain receptor changes found with regular smoking tend toward normalization with smoking reduction and cessation.…”

Greater Nicotinic Acetylcholine Receptor Density in Smokers Than in Nonsmokers: A PET Study with 2-18F-FA-85380

“…In addition, the SPM analysis revealed that no brain region exhibited the opposite condition (i.e., V T /f P in nonsmoker > V T /f P in smoker). These observations were consistent with several reports of greater receptor densities in smokers than in nonsmokers in studies of postmortem tissue (5,6) and results from in vivo studies (28–30). We observed the greatest differences in V T /f P in the cerebellum and midbrain, with frontal cortex and pons also showing differences.…”

β2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking

“…Additionally, they reported significantly lower β 2 *-nAChR availability at 21 days of abstinence compared to 10 days of abstinence. One difference is that the previous study18 had significantly lower β 2 *-nAChR availability in all regions at 4 hr of abstinence compared to the nonsmokers, while the current study reports lower thalamic but similar β 2 *-nAChR availability in the striatum, cerebellum and throughout the cortex compared to the nonsmoker group at 1 day of abstinence. This is interesting and likely due to high levels of residual nicotine or metabolites present in the brain at 4 hr of abstinence (versus ∼24 hours in the current study) resulting in lower β 2 *-nAChR availability.…”

“…This study is also consistent with a previous study18 demonstrating that higher β 2 *-nAChR availability in recently abstinent tobacco smokers compared to nonsmokers is temporary. In the previous study in men, β 2 *-nAChR availability decreased to nonsmoker levels in some subjects by 21 days of abstinence.…”

“…This may be because of the older average age (approximately 5 years) of participants in the current study, because ␤ 2 *-nAChR availability has been shown to decrease with age in nonsmokers. 77 This study and previous in vivo positron emission tomography 78 and SPECT 8,18 studies report no upregulation of thalamic ␤ 2 *-nAChR availability during acute abstinence, which conflicts with the findings of postmortem 2 and animal 8,79 studies. In general, this may be because of differences in methods or the higher relative dose of nicotine in the postmortem and animal studies.…”

Treatment for Tobacco Dependence: Effect on Brain Nicotinic Acetylcholine Receptor Density

“…No associations between a 4 b 2 * nAChR densities and treatment type were found, but significant associations were discovered between the extent of a 4 b 2 * nAChR density reduction and the amount of decreased cigarette usage. These results indicate that a 4 b 2 * nAChR density is strongly linked to the number of cigarettes smoked per day, but not to the treatment type being administered, and are consistent with our previous study of untreated smokers (Brody et al, 2013) and other studies linking nicotine (Marks et al, 2011;Yates et al, 1995;Zhang et al, 2002) and cigarette smoke (Mamede et al, 2007;Mukhin et al, 2008;Staley et al, 2006;Wullner et al, 2008) exposure with upregulation of a 4 b 2 * nAChRs in brain regions other than the thalamus. Because education about the biological effects of smoking and quitting smoking are standard parts of smoking-cessation psychotherapy (Fiore et al, 2008), the additional information found here could prove useful in treatment of smokers by letting them know that brain receptor changes found with regular smoking tend toward normalization with smoking reduction and cessation.…”

Greater Nicotinic Acetylcholine Receptor Density in Smokers Than in Nonsmokers: A PET Study with 2-18F-FA-85380

“…In addition, the SPM analysis revealed that no brain region exhibited the opposite condition (i.e., V T /f P in nonsmoker > V T /f P in smoker). These observations were consistent with several reports of greater receptor densities in smokers than in nonsmokers in studies of postmortem tissue (5,6) and results from in vivo studies (28–30). We observed the greatest differences in V T /f P in the cerebellum and midbrain, with frontal cortex and pons also showing differences.…”

β2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking

“…Additionally, they reported significantly lower β 2 *-nAChR availability at 21 days of abstinence compared to 10 days of abstinence. One difference is that the previous study18 had significantly lower β 2 *-nAChR availability in all regions at 4 hr of abstinence compared to the nonsmokers, while the current study reports lower thalamic but similar β 2 *-nAChR availability in the striatum, cerebellum and throughout the cortex compared to the nonsmoker group at 1 day of abstinence. This is interesting and likely due to high levels of residual nicotine or metabolites present in the brain at 4 hr of abstinence (versus ∼24 hours in the current study) resulting in lower β 2 *-nAChR availability.…”

“…This study is also consistent with a previous study18 demonstrating that higher β 2 *-nAChR availability in recently abstinent tobacco smokers compared to nonsmokers is temporary. In the previous study in men, β 2 *-nAChR availability decreased to nonsmoker levels in some subjects by 21 days of abstinence.…”

“…This may be because of the older average age (approximately 5 years) of participants in the current study, because ␤ 2 *-nAChR availability has been shown to decrease with age in nonsmokers. 77 This study and previous in vivo positron emission tomography 78 and SPECT 8,18 studies report no upregulation of thalamic ␤ 2 *-nAChR availability during acute abstinence, which conflicts with the findings of postmortem 2 and animal 8,79 studies. In general, this may be because of differences in methods or the higher relative dose of nicotine in the postmortem and animal studies.…”

Treatment for Tobacco Dependence: Effect on Brain Nicotinic Acetylcholine Receptor Density

“…No associations between a 4 b 2 * nAChR densities and treatment type were found, but significant associations were discovered between the extent of a 4 b 2 * nAChR density reduction and the amount of decreased cigarette usage. These results indicate that a 4 b 2 * nAChR density is strongly linked to the number of cigarettes smoked per day, but not to the treatment type being administered, and are consistent with our previous study of untreated smokers (Brody et al, 2013) and other studies linking nicotine (Marks et al, 2011;Yates et al, 1995;Zhang et al, 2002) and cigarette smoke (Mamede et al, 2007;Mukhin et al, 2008;Staley et al, 2006;Wullner et al, 2008) exposure with upregulation of a 4 b 2 * nAChRs in brain regions other than the thalamus. Because education about the biological effects of smoking and quitting smoking are standard parts of smoking-cessation psychotherapy (Fiore et al, 2008), the additional information found here could prove useful in treatment of smokers by letting them know that brain receptor changes found with regular smoking tend toward normalization with smoking reduction and cessation.…”