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

Mamede, Marcelo; Ishizu, Koji; Ueda, Masashi; Mukai, Takahiro; Iida, Yasuhiko; Kawashima, Hidekazu; Fukuyama, Hidenao; Togashi, Kaori; Saji, Hideo

doi:10.2967/jnumed.107.043471

Cited by 80 publications

(73 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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.…”

Section: Discussionsupporting

confidence: 80%

“…ROIs were the prefrontal cortex, brainstem, and cerebellum, which were chosen for three reasons. First and most importantly, previous reports indicate that these ROIs (and most brain regions other than the thalamus) have upregulation of nAChR densities in cigarette smokers (Brody et al, 2013;Mamede et al, 2007;Mukhin et al, 2008;Staley et al, 2006;Wullner et al, 2008). Second, these ROIs have a range of 2-FA-binding levels from moderate to high (Brody et al, 2006;Brody et al, 2013;Kimes et al, 2008;Mukhin et al, 2008), which eliminates the issues of examining the highest nAChR density region (thalamus) as an experimental variable (because it does not have upregulation of nAChRs in smokers), and ROIs with very low nAChR density (eg, corpus callosum), which may have very small differences between groups or conditions.…”

Section: Pet Image Analysismentioning

confidence: 99%

“…In follow-up scanning, nAChR upregulation in smokers was found to normalize to levels of non-smokers when participants were given contingency management to maintain abstinence for roughly 3 (Mamede et al, 2007) to 12 (Cosgrove et al, 2009) weeks. However, to our knowledge, no one has yet reported the effects of commonly used, standard first-line treatments for cigarette smoking on nAChR density.…”

Section: Introductionmentioning

confidence: 99%

“…Previous brain imaging studies of human smokers, including a recent one by our group, have used positron emission tomography (PET) or single photon emission computed tomography to demonstrate upregulation of nAChRs in smokers compared with non-smoking controls in brain regions other than the thalamus (Brody et al, 2013;Cosgrove et al, 2009;Mamede et al, 2007;Mukhin et al, 2008;Staley et al, 2006;Wullner et al, 2008). In follow-up scanning, nAChR upregulation in smokers was found to normalize to levels of non-smokers when participants were given contingency management to maintain abstinence for roughly 3 (Mamede et al, 2007) to 12 (Cosgrove et al, 2009) weeks.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Brody

Mukhin

Shulenberger

et al. 2013

Neuropsychopharmacol

View full text Add to dashboard Cite

Cigarette smoking leads to upregulation of brain nicotinic acetylcholine receptors (nAChRs), including the common a 4 b 2 * nAChR subtype. Although a substantial percentage of smokers receive treatment for tobacco dependence with counseling and/or medication, the effect of a standard course of these treatments on nAChR upregulation has not yet been reported. In the present study, 48 otherwise healthy smokers underwent positron emission tomography (PET) scanning with the radiotracer 2-FA (for labeling a 4 b 2 * nAChRs) before and after treatment with either cognitive-behavioral therapy, bupropion HCl, or pill placebo. Specific binding volume of distribution (V S /f P ), a measure proportional to a 4 b 2 * nAChR density, was determined for regions known to have nAChR upregulation with smoking (prefrontal cortex, brainstem, and cerebellum). In the overall study sample, significant decreases in V S /f P were found for the prefrontal cortex, brainstem, and cerebellum of À 20 (±35), À 25 (±36), and À 25 (±31)%, respectively, which represented movement of V S /f P values toward values found in non-smokers (mean 58.2% normalization of receptor levels). Participants who quit smoking had significantly greater reductions in V S /f P across regions than non-quitters, and correlations were found between reductions in cigarettes per day and decreases in V S /f P for brainstem and cerebellum, but there was no between-group effect of treatment type. Thus, smoking reduction and cessation with commonly used treatments (and pill placebo) lead to decreased a 4 b 2 * nAChR densities across brain regions. Study findings could prove useful in the treatment of smokers by providing encouragement with the knowledge that decreased smoking leads to normalization of specific brain receptors.

show abstract

Section: Discussionsupporting

confidence: 80%

Section: Pet Image Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Brody

Mukhin

Shulenberger

et al. 2013

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…177 Upregulation following smoking cessation is time dependent, and 3 weeks later nAChRs were downregulated to the levels of nonsmokers. 178 The possible contribution of nAChR upregulation to the pathophysiology of ND is not fully understood, but is believed to be mediated by midbrain DA release. Vezina et al 168 have proposed that nicotine exposure produces temporary nAChR upregulation, leading to augmentation of midbrain dopaminergic neuron excitation and the induction of long-term potentiation.…”

Section: General Overviewmentioning

confidence: 99%

Differential contribution of genetic variation in multiple brain nicotinic cholinergic receptors to nicotine dependence: recent progress and emerging open questions

Greenbaum¹,

Lerer²

2009

Mol Psychiatry

View full text Add to dashboard Cite

Nicotine dependence (ND), a major public health challenge, is a complex, multifactorial behavior, in which both genetic and environmental factors have a role. Brain nicotinic acetylcholine receptor (nAChR)-encoding genes are among the most prominent candidate genes studied in the context of ND, because of their biological relevance as binding sites for nicotine. Until recently, most research on the role of nAChRs in ND has focused on two of these genes (encoding the a4-and b2-subunits) and not much attention has been paid to the possible contribution of the other nine brain nAChR subunit genes (a2-a3, a5-a7, a9-a10, b3-b4) to the pathophysiology and genetics of ND. This situation has changed dramatically in the last 2 years during which intensive research had addressed the issue, mainly from the genetics perspective, and has shown the importance of the CHRNA5-CHRNA3-CHRNB4 and CHRNA6-CHRNB3 loci in ND-related phenotypes. In this review, we highlight recent findings regarding the contribution of non-a4/b2-subunit containing nAChRs to ND, based on several lines of evidence: (1) human genetics studies (including linkage analysis, candidate-gene association studies and whole-genome association studies) of several ND-related phenotypes; (2) differential pharmacological and biochemical properties of receptors containing these subunits; (3) evidence from genetically manipulated mice; and (4) the contribution of nAChR genes to ND-related personality traits and neurocognitive profiles. Combining neurobiological genetic and behavioral perspectives, we suggest that genetic susceptibility to ND is not linked to one or two specific nAChR subtype genes but to several. In particular, the a3, a5-6 and b3-4 nAChR subunit-encoding genes may play a much more pivotal role in the neurobiology and genetics of ND than was appreciated earlier. At the functional level, variants in these subunit genes (most likely regulatory) may have independent as well as interactive contributions to the ND phenotype spectrum. We address methodological challenges in the field, highlight open questions and suggest possible pathways for future research.

show abstract

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

Cosgrove¹,

Batis²,

Bois³

et al. 2009

Arch Gen Psychiatry

150

108

View full text Add to dashboard Cite

Context β2*-nicotinic acetylcholine receptor (β2*-nAChR) availability is higher in recently abstinent smokers compared to never smokers. Variations in β2*-nAChR availability over the course of abstinence may be related to the urge to smoke, the extent of nicotine withdrawal and successful abstinence. Objective To examine changes in β2*-nAChR availability during acute and prolonged abstinence from tobacco smoking and to determine how changes in β2*-nAChR availability were related to clinical features of tobacco smoking. Design Tobacco smokers participated in up to 4 [123I]5-IA-85380 ([123I]5-IA) single photon emission computed tomography (SPECT) scans during abstinence: 1 day (n=7), 1 week (n=17), 2 weeks (n=7), 4 weeks (n=11), and 6-12 weeks (n=6). Age-matched nonsmokers participated in 1 [123I]5-IA SPECT scan. All subjects completed 1 magnetic resonance imaging study. Setting Academic imaging center. Participants Tobacco smokers (n=19) and an age-matched nonsmoker comparison group (n=20). Main Outcome Measure [123I]5-IA SPECT images were converted to distribution volume and were analyzed using regions of interest. Results Compared to nonsmokers, β2*-nAChR availability in the striatum, cortex and cerebellum of smokers was not different at one day of abstinence, significantly higher at 1week of abstinence and not different at 4 or 6-12 weeks of abstinence. In smokers, at 6-12 weeks of abstinence, β2*-nAChR availability was significantly lower in the cortex and cerebellum compared to 1 week of abstinence. Additionally, cerebellar β2*-nAChR availability at 4 weeks of abstinence was positively correlated with craving on the day of scan. Conclusions These data suggest higher β2*-nAChR availability persists up to 1 month of abstinence, and normalizes to nonsmoker levels by 6-12 weeks of abstinence from tobacco smoking. These marked and persistent changes in β2*-nAChR availability may contribute to difficulties with tobacco cessation.

show abstract

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

Cited by 80 publications

References 26 publications

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

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

Differential contribution of genetic variation in multiple brain nicotinic cholinergic receptors to nicotine dependence: recent progress and emerging open questions

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

Contact Info

Product

Resources

About