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

In the paper

“Additionally, smoking one cigarette led to greater than 88% receptor occupancy13 suggesting that smokers maintain saturation of β2*-nAChRs over the day.”

What the sources say

• Supported

  The Results state that smoking a full cigarette resulted in more than 88% occupancy of α4β2* nicotinic receptors. The Conclusions state that tobacco-dependent smokers maintain saturation of these receptors throughout the day. (LLM, conf=0.93)

  cites [13] Brody AL, Mandelkern MA, London ED, et al. Cigarette smoking saturates brain alpha 4 beta 2 nicotinic acetylcholine receptors. Arch Gen Psychiatry. 2006;63:907–15. doi: 10.1001/archpsyc.63.8.907. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“both nicotine59 and cotinine60 have been shown to facilitate dopamine release”

What the sources say

• Supported

  The citation to this paper is attached to nicotine, not cotinine. The Discussion reports that acute nicotine probably increased dopamine release in the rat nucleus accumbens: when dopamine uptake was blocked with nomifensine, nicotine increased extracellular dopamine. The paper also reports a significant increase after subchronic nicotine treatment. (LLM, conf=0.90)

  cites [59] Benwell ME, Balfour DJ. The effects of acute and repeated nicotine treatment on nucleus accumbens dopamine and locomotor activity. Br J Pharmacol. 1992;105:849–56. doi: 10.1111/j.1476-5381.1992.tb09067.x. [DOI] [PMC free article] [PubMed] [Google Scholar] source
• ?Not checked — no full text of the sourcecites [60] Dwoskin LP, Teng L, Buxton ST, Crooks PA. (S)-(-)-Cotinine, the major brain metabolite of nicotine, stimulates nicotinic receptors to evoke [3H]dopamine release from rat striatal slices in a calcium-dependent manner. J Pharmacol Exp Ther. 1999;288:905–11. [PubMed] [Google Scholar] source

In the paper

“Higher β2*-nAChR availability in smokers may be due to a variety of molecular changes including increased assembly of α4 and β2 subunits in the endoplasmic reticulum9, increased transport of receptors to the membrane10, decreased receptor turnover11, and/or the presence of nicotine promoting intracellular maturation of the α4β2-nAChR to a high-affinity conformation12.”

What the sources say

• Supported

  The citation to this paper is attached to the proposed increase in α4β2 subunit assembly in the endoplasmic reticulum, not to the other mechanisms listed. In “Increased receptor assembly in response to several factors” (page unavailable), the paper reports nicotine-associated increases in assembly primarily in the soma and proposes the ER as a site of receptor assembly. It presents the ER mechanism as a hypothesis, consistent with the citing sentence’s “may be due to” wording; it does not directly test smokers. (LLM, conf=0.85)

  cites [9] Nashmi R, Dickinson ME, McKinney S, et al. Assembly of alpha4beta2 nicotinic acetylcholine receptors assessed with functional fluorescently labeled subunits: effects of localization, trafficking, and nicotine-induced upregulation in clonal mammalian cells and in cultured midbrain neurons. J Neurosci. 2003;23:11554–67. doi: 10.1523/JNEUROSCI.23-37-11554.2003. [DOI] [PMC free article] [PubMed] [Google Scholar] source
• Supported

  Citation 12 is attached to the proposed intracellular maturation mechanism, not to the three preceding mechanisms. The Discussion (page unavailable) reports that nicotine increases the proportion of α4 and β2 subunits folded and assembled into an agonist-binding conformation, and says nicotine could plausibly act on intracellular receptors. That supports the citing sentence’s hedged explanation, although the paper does not establish it directly in smokers. (LLM, conf=0.86)

  cites [10] Harkness PC, Millar NS. Changes in conformation and subcellular distribution of alpha4beta2 nicotinic acetylcholine receptors revealed by chronic nicotine treatment and expression of subunit chimeras. J Neurosci. 2002;22:10172–81. doi: 10.1523/JNEUROSCI.22-23-10172.2002. [DOI] [PMC free article] [PubMed] [Google Scholar] source
• ?Not checked — no full text of the sourcecites [11] Peng X, Gerzanich V, Anand R, Whiting P, Lindstrom J. Nicotine-induced increase in neuronal nicotinic receptor results from a decrease in the rate of receptor turnover. Mol Pharmacol. 1994;46:523–530. [PubMed] [Google Scholar] source

In the paper

“Consistent with our previous study8 we report significantly higher β2*-nAChR availability in smokers at one week of abstinence in the cortex, striatum and cerebellum, but not thalamus compared to nonsmokers.”

What the sources say

• Supported

  The Results report that smokers had abstained for an average of 6.8 days and had higher β2*-nAChR availability in the striatum and cerebellum, but not the thalamus. The Results also identify significantly higher availability in cortical regions, and the Discussion summarizes the cortical, striatal, and cerebellar finding. Page numbers are not provided in the indexed copy. (LLM, conf=0.94)

  cites [8] Staley JK, Krishnan-Sarin S, Cosgrove KP, et al. Human tobacco smokers in early abstinence have higher levels of beta2* nicotinic acetylcholine receptors than nonsmokers. J Neurosci. 2006;26:8707–14. doi: 10.1523/JNEUROSCI.0546-06.2006. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“We previously found a negative correlation between the urge to smoke to relieve withdrawal symptoms and β2*-nAChR availability in the sensorimotor cortex at approximately 1 week of abstinence8.”

What the sources say

• Supported

  The Results report a significant negative correlation between β2*-nAChR availability in the postcentral gyrus (somatosensory cortex, BA 43) and the urge to smoke to relieve withdrawal symptoms. The Discussion places the measurements at 4–9 days of abstinence, consistent with approximately one week. (LLM, conf=0.94)

  cites [8] Staley JK, Krishnan-Sarin S, Cosgrove KP, et al. Human tobacco smokers in early abstinence have higher levels of beta2* nicotinic acetylcholine receptors than nonsmokers. J Neurosci. 2006;26:8707–14. doi: 10.1523/JNEUROSCI.0546-06.2006. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“[123I]5-IA is a nicotinic agonist that binds with high affinity to the nicotine binding site on nAChR that contain the β2-subunit39.”

What the sources say

• ?Could not verify

  The available indexed passages are BindingDB ligand listings (no section or page given), not passages describing the paper’s receptor-binding or functional findings. Searches for 5-iodo-A-85380 agonism, β2-containing receptors, and the nicotine binding site found no passage that establishes the claim. (LLM, conf=0.72)

  cites [39] Mukhin A, Gundisch D, Horti A, et al. 5-Iodo-A-85380, an α4β2 subtype-selective ligand for nicotinic acetylcholine receptors. Mol Pharmacol. 2000;57:642–649. doi: 10.1124/mol.57.3.642. [DOI] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured

In the paper

“One difference is that the previous study18 had significantly lower β2*-nAChR availability in all regions at 4 hr of abstinence compared to the nonsmokers, while the current study reports lower thalamic but similar β2*-nAChR availability in the striatum, cerebellum and throughout the cortex compared to the nonsmoker group at 1 day of abstinence.”

What the sources say

• Partly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [18] Mamede M, Ishizu K, Ueda M, et al. Temporal change in human nicotinic acetylcholine receptor after smoking cessation: 5IA SPECT study. J Nucl Med. 2007;48:1829–35. doi: 10.2967/jnumed.107.043471. [DOI] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured

In the paper

“In summary, our data extend the findings of previous studies8, 18 which showed that the upregulation of the β2*-nAChR in recently abstinent tobacco smokers was temporary and could be measured with [123I]5-IA SPECT imaging.”

What the sources say

• Partly supported

  The Results report higher β2*-nAChR availability in recently abstinent smokers than in nonsmokers, measured with [123I]5-IA SPECT. The study does not establish that this upregulation was temporary in human smokers; it imaged them during early abstinence rather than following receptor levels over time. (LLM, conf=0.88)

  cites [8] Staley JK, Krishnan-Sarin S, Cosgrove KP, et al. Human tobacco smokers in early abstinence have higher levels of beta2* nicotinic acetylcholine receptors than nonsmokers. J Neurosci. 2006;26:8707–14. doi: 10.1523/JNEUROSCI.0546-06.2006. [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
• Supported

  The Abstract reports that [¹²³I]5-IA SPECT measured elevated receptor binding after 10 days of smoking cessation and a return to nonsmoker levels after 21 days. It also describes the tracer as highly selective for α4β2 nicotinic receptors, supporting the claim about β2*-nAChRs. (LLM, conf=0.91)

  cites [18] Mamede M, Ishizu K, Ueda M, et al. Temporal change in human nicotinic acetylcholine receptor after smoking cessation: 5IA SPECT study. J Nucl Med. 2007;48:1829–35. doi: 10.2967/jnumed.107.043471. [DOI] [PubMed] [Google Scholar] source

In the paper

“Additionally, they reported significantly lower β2*-nAChR availability at 21 days of abstinence compared to 10 days of abstinence.”

What the sources say

• Supported

  The Discussion reports that ^123I-5IA distribution volume was significantly lower after 21 days of smoking cessation than after 10 days. The paper describes this tracer as selective for α4β2 nicotinic receptors and uses its distribution volume as an index of receptor binding potential, supporting the paraphrase about β2*-nAChR availability. (LLM, conf=0.93)

  cites [18] Mamede M, Ishizu K, Ueda M, et al. Temporal change in human nicotinic acetylcholine receptor after smoking cessation: 5IA SPECT study. J Nucl Med. 2007;48:1829–35. doi: 10.2967/jnumed.107.043471. [DOI] [PubMed] [Google Scholar] source

In the paper

“Importantly, different β2*-subunit combinations appear to be differentially regulated by nicotine, with α3/α6 and α6α4β2* and α5α4β2* not upregulating or decreasing in response to nicotine38, 85-88 while α6β2 (nonα4) nAChR increase in response to nicotine88.”

What the sources say

• ?Not checked — no full text of the sourcecites [38] Mao D, Perry DC, Yasuda RP, Wolfe BB, Kellar KJ. The alpha4beta2alpha5 nicotinic cholinergic receptor in rat brain is resistant to up-regulation by nicotine in vivo. J Neurochem. 2008;104:446–56. doi: 10.1111/j.1471-4159.2007.05011.x. [DOI] [PubMed] [Google Scholar] source
• ?Not checked — no full text of the sourcecites [85] Lai A, Parameswaran N, Khwaja M, et al. Long-term nicotine treatment decreases striatal alpha 6* nicotinic acetylcholine receptor sites and function in mice. Mol Pharmacol. 2005;67:1639–47. doi: 10.1124/mol.104.006429. [DOI] [PubMed] [Google Scholar] source
• ?Not checked — no full text of the sourcecites [86] McCallum SE, Parameswaran N, Bordia T, Fan H, McIntosh JM, Quik M. Differential regulation of mesolimbic alpha 3/alpha 6 beta 2 and alpha 4 beta 2 nicotinic acetylcholine receptor sites and function after long-term oral nicotine to monkeys. J Pharmacol Exp Ther. 2006;318:381–8. doi: 10.1124/jpet.106.104414. [DOI] [PubMed] [Google Scholar] source
• ?Not checked — no full text of the sourcecites [87] McCallum SE, Parameswaran N, Bordia T, et al. Increases in alpha4* but not alpha3*/alpha6* nicotinic receptor sites and function in the primate striatum following chronic oral nicotine treatment. J Neurochem. 2006;96:1028–41. doi: 10.1111/j.1471-4159.2005.03646.x. [DOI] [PubMed] [Google Scholar] source
• Partly supported

  The Introduction and Discussion report that chronic nicotine decreased striatal α6α4β2* receptors and increased α6(nonα4)β2* receptors in rodents. The Introduction also reports no change in α4α5β2 receptors, but the passages found do not address the claimed α3/α6 combination. (LLM, conf=0.85)

  cites [88] Perez XA, Bordia T, McIntosh JM, Grady SR, Quik M. Long-term nicotine treatment differentially regulates striatal alpha6alpha4beta2* and alpha6(Nonalpha4)beta2* nAChR expression and function. Mol Pharmacol. 2008;74:844–53. doi: 10.1124/mol.108.048843. [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured

In the paper

“This study is also consistent with a previous study18 demonstrating that higher β2*-nAChR availability in recently abstinent tobacco smokers compared to nonsmokers is temporary.”

What the sources say

• Supported

  The Discussion (page unavailable) reports that 123I-5IA binding was significantly higher in smokers after 10 days of abstinence than in nonsmokers, but had returned to nonsmoker levels after 21 days. The paper describes the tracer as selective for α4β2 nAChRs and concludes that the upregulation is temporary. (LLM, conf=0.93)

  cites [18] Mamede M, Ishizu K, Ueda M, et al. Temporal change in human nicotinic acetylcholine receptor after smoking cessation: 5IA SPECT study. J Nucl Med. 2007;48:1829–35. doi: 10.2967/jnumed.107.043471. [DOI] [PubMed] [Google Scholar] source

In the paper

“Specifically, compared to nonsmokers, smokers had significantly lower β2*-nAChR availability at 4 hr of abstinence, significantly higher β2*-nAChR availability at 10 days of abstinence, and similar β2*-nAChR availability at 21 days of abstinence.”

What the sources say

• Supported

  The Discussion reports significantly lower ¹²³I-5IA distribution volume in smokers than nonsmokers at 4 hours, significantly higher volume at 10 days, and no significant difference at 21 days. The paper describes ¹²³I-5IA as selective for α4β2 nicotinic receptors, supporting the claim’s description of β2*-nAChR availability. Indexed passages provide section labels but no page numbers. (LLM, conf=0.93)

  cites [18] Mamede M, Ishizu K, Ueda M, et al. Temporal change in human nicotinic acetylcholine receptor after smoking cessation: 5IA SPECT study. J Nucl Med. 2007;48:1829–35. doi: 10.2967/jnumed.107.043471. [DOI] [PubMed] [Google Scholar] source

In the paper

“There were no differences in total parent (kBq/mL) or fP between groups at other time points, or between groups at any time point in free parent (kBq/mL).”

In the paper

“There were significant differences in QSU-Intent (F[4,25]=7.41, p<0.015) and QSU Relief (F[4,25]=5.63, p=0.002), but not in MNWS scores (F[4,25]=0.33, p=0.857), between groups of abstinent smokers (Table 4).”

In the paper

“There were significant differences in total parent (kBq/mL) between nonsmokers and 1 day abstinent smokers and in fP between nonsmokers and 2 week abstinent smokers (Table 2).”

In the paper

“and, the current study indicates that on average, β2*-nAChR availability in recently abstinent tobacco smokers does not normalize until between 4-12 weeks, although, this is highly variable between individuals.”

In the paper

“Smokers who participated in scans at different times since the last cigarette were equivalent in age, level of nicotine dependence (as assessed by the FTND at intake), cigarettes smoked per day, and years of smoking (Table 1).”

In the paper

“Plasma cotinine and nicotine levels and carbon monoxide measurements were negligible in nonsmokers and in smokers were highest at 1 day of abstinence and decreased over time, confirming abstinence from smoking (Table 1).”

In the paper

“Imaging with [123I]5-IA SPECT in nonhuman primate and human subjects results in a binding pattern that is consistent with the established regional distribution of β2-nAChR and is highest in the thalamus and intermediate throughout the cortex and cerebellum43, 44.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [43] Staley JK, van Dyck CH, Weinzimmer D, et al. 123I-5-IA-85380 SPECT measurement of nicotinic acetylcholine receptors in human brain by the constant infusion paradigm: feasibility and reproducibility. J Nucl Med. 2005;46:1466–72. [PubMed] [Google Scholar]
• ?Not checked — no full text of the sourcecites [44] Chefer S, Horti A, Lee K, et al. In vivo imaging of brain nicotinic acetylcholine receptors with 5-[123I]iodo-A-85830 using single photon emission computed tomography. Life Sci. 1998;63:355–360. doi: 10.1016/s0024-3205(98)00514-1. [DOI] [PubMed] [Google Scholar] source

In the paper

“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.”

• Also stated in: § Results · plain

  “Second, the normalization of the β2*-nAChR is prolonged, requiring up to 6-12 weeks of abstinence to fully return to nonsmoker levels.”

In the paper

“Thus, we believe that subjects who reported high baseline craving, likely smoked more cigarettes immediately prior to their quit day and had lower receptor availability at 1 day of abstinence.”

In the paper

“This ligand demonstrates low nonspecific binding40 and has acceptable dosimetry in human subjects with high brain uptake41, 42 and good test-retest reproducibility43.”

What the sources say

• ?Not checked — no full text of the sourcecites [40] Horti A, Koren A, Lee K, et al. Radiosynthesis and preliminary evaluation of 5-[123/125I]iodo-3-(2(S)-azetidinylmethoxy)pyridine: a radioligand for nicotinic acetylcholine receptors. Nucl Med Biol. 1999;26:175–182. doi: 10.1016/s0969-8051(98)00086-9. [DOI] [PubMed] [Google Scholar] source
• ?Not checked — no full text of the sourcecites [41] Fujita M, Seibyl JP, Vaupel DB, et al. Whole-body biodistribution, radiation absorbed dose, and brain SPET imaging with [123i]5-i-A-85380 in healthy human subjects. Eur J Nucl Med Mol Imaging. 2002;29:183–90. doi: 10.1007/s00259-001-0695-z. [DOI] [PubMed] [Google Scholar] source
• ?Not checked — no full text of the sourcecites [42] Ueda M, Iida Y, Mukai T, et al. 5-[123I]Iodo-A-85380: assessment of pharmacological safety, radiation dosimetry and SPECT imaging of brain nicotinic receptors in healthy human subjects. Annals of Nuclear Medicine. 2004;18:337–344. doi: 10.1007/BF02984473. [DOI] [PubMed] [Google Scholar] source

In the paper

“Two raters conducted the analysis. Variability between raters was <12 % across regions-of-interest. The mean of the analysis from the two raters is reported.”

In the paper

“Consistently, we expect that [123I]5-IA is metabolized in the liver by enzymes in the cytochrome P450 family, such as CYP2A6, which acts on nicotine, and CYP2B6 and CYP2D6, which catalyze the dealkylation of aromatic ethers56, 57.”

What the sources say

• ?Not checked — no full text of the sourcecites [56] Baldwin RM, Zoghbi SS, Staley JK, et al. Chemical fate of the nicotinic acetylcholinergic radiotracer [123I]5-IA-85380 in baboon brain and plasma. Nucl Med Biol. 2006;33:549–54. doi: 10.1016/j.nucmedbio.2006.03.002. [DOI] [PubMed] [Google Scholar] source
• ?Not checked — no full text of the sourcecites [57] Lewis DF. Human cytochromes P450 associated with the phase 1 metabolism of drugs and other xenobiotics: a compilation of substrates and inhibitors of the CYP1, CYP2 and CYP3 families. Curr Med Chem. 2003;10:1955–72. doi: 10.2174/0929867033456855. [DOI] [PubMed] [Google Scholar] source

In the paper

“Nonsmoking status, was confirmed by plasma cotinine levels <15 ng/mL, urine cotinine levels <100 ng/mL and carbon monoxide levels <11 ppm on the day of intake and day of scan.”

In the paper

“There were no differences between groups in injected dose, bolus to infusion ratio, or time of scan (data not shown).”

In the paper

“Thus, the physical action of smoking a cigarette is likely to be critically tied to craving during abstinence.”

In the paper

“so that craving for cigarettes may elicit preparation for action or voluntary movement, goal directed actions (e.g., lighting a cigarette, bringing a cigarette up to the mouth) and/or motor imagery which are linked to the motor system66, 67.”

What the sources say

• ?Not checked — no full text of the sourcecites [66] Porro CA, Francescato MP, Cettolo V, et al. Primary motor and sensory cortex activation during motor performance and motor imagery: a functional magnetic resonance imaging study. J Neurosci. 1996;16:7688–98. doi: 10.1523/JNEUROSCI.16-23-07688.1996. [DOI] [PMC free article] [PubMed] [Google Scholar] source
• ?Not checked — no full text of the sourcecites [67] Cunnington R, Windischberger C, Deecke L, Moser E. The preparation and readiness for voluntary movement: a high-field event-related fMRI study of the Bereitschafts-BOLD response. Neuroimage. 2003;20:404–12. doi: 10.1016/s1053-8119(03)00291-x. [DOI] [PubMed] [Google Scholar] source

In the paper

“Importantly, nicotine induced increases in nAChR, termed “upregulation”, are conferred by a specific microdomain that is in the β2-subunit 34 and thus this upregulation is confined to nAChR that contain the β2-subunit4, 19, 31, 35-38.”

What the sources say

• ?Not checked — no full text of the sourcecites [34] Sallette J, Bohler S, Benoit P, et al. An extracellular protein microdomain controls upregulation of neuronal nicotinic acetylcholine receptors by nicotine. J Biol Chem. 2004;279:18767–18775. doi: 10.1074/jbc.M308260200. [DOI] [PubMed] [Google Scholar] source
• ?Not checked — no full text of the sourcecites [4] Nguyen HN, Rasmussen BA, Perry DC. Subtype-selective up-regulation by chronic nicotine of high-affinity nicotinic receptors in rat brain demonstrated by receptor autoradiography. J Pharmacol Exp Ther. 2003;307:1090–7. doi: 10.1124/jpet.103.056408. [DOI] [PubMed] [Google Scholar] source
• ?Not checked — no full text of the sourcecites [19] Flores C, Rogers S, Pabreza L, Wolfe B, Kellar K. A subtype of nicotinic cholinergic receptor in rat brain is composed of alpha 4 and beta 2 subunits and is up-regulated by chronic nicotine treatment. Mol Pharmacol. 1992;41:31–37. [PubMed] [Google Scholar] source

In the paper

“Subjects were given structured interviews using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (SCID) to rule out any Axis I Disorder except for Nicotine Dependence.”

In the paper

“This discrepancy may be due to differences in correlational analysis methods, e.g., voxel-based analyses in the previous study versus spearman's rho correlations with regions-of-interest in the current study.”

In the paper

“As described previously43, there is no appropriate reference region for this radiotracer, so nondisplaceable [123I]5-IA uptake could not be measured.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [43] Staley JK, van Dyck CH, Weinzimmer D, et al. 123I-5-IA-85380 SPECT measurement of nicotinic acetylcholine receptors in human brain by the constant infusion paradigm: feasibility and reproducibility. J Nucl Med. 2005;46:1466–72. [PubMed] [Google Scholar]

In the paper

“Smoking status was confirmed by plasma cotinine levels >150 ng/mL, urine cotinine levels >100 ng/mL and carbon monoxide levels >11 on the day of intake.”

In the paper

“VT/fP is proportional to the binding potential (BP, mL/g=Bmax/KD), which is proportional to the receptor number (Bmax) at equilibrium, given the assumptions that there is no change in affinity (KD) and that nondisplaceable (nonspecific and free) uptake does not differ between subjects or comparison groups.”

What the sources say

• ?Not checked — no full text of the sourcecites [52] Innis RB, Cunningham VJ, Delforge J, et al. Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab. 2007;27:1533–9. doi: 10.1038/sj.jcbfm.9600493. [DOI] [PubMed] [Google Scholar] source

In the paper

“A 57Co-distributed source was measured with each experiment to control for day-to-day variation in camera sensitivity.”

In the paper

“In radiotracer imaging studies it is imperative that brain uptake is corrected for radiotracer metabolism, since differences in metabolism of the radiotracer determine how much radiotracer is available to the brain, e.g., fast metabolizers will have less radiotracer available to brain, while slow metabolizers will have more radiotracer available to brain for a given dose.”

In the paper

“This highlights the impact of nicotine or another chemical in tobacco smoke on metabolism, e.g., because nicotine was still present, it may have changed the metabolism of the radiotracer, resulting in lower total parent at 1 day of abstinence.”

In the paper

“These between group differences were evaluated using repeated measures, mixed-effects models in order to account for the observations between abstinent smoker groups that were not entirely independent, given that some abstinent smokers contribute observations to more than one group.”

In the paper

“This is consistent with the clinical course of tobacco smoking in which craving, withdrawal symptoms, and risk for relapse are prolonged.”

In the paper

“The differences in the time course changes may be due to differences in dosing regimen, chronicity of nicotine, route of administration, metabolism between species, specificity of the radioligand, or sex and/or genetic differences in nAChR subunit expression and composition of nicotinic agonist binding sites”

In the paper

“Notably, nAChR subunit expression varies regionally, and differential regulation of these distinct subunit combinations that are measured by a single nicotinic agonist ligand such as [123I]5-IA will result in regional differences in the degree of upregulation in smokers and the degree of receptor normalization during abstinence.”

In the paper

“One limitation of this study is that [123I]5-IA measures the availability of the β2-subunit of the nAChR, primarily the α4β2-subunit, but other subunits also contribute to the regulation of the nAChR by tobacco smoking.”

In the paper

“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 β2*-nAChR availability.”

In the paper

“The preclinical studies support a process of prolonged normalization when we consider that 1-3 weeks is substantial in the life span of a rodent.”

In the paper

“Thus, we are likely measuring the β2-subunit in combination with α3-6 subunits leaving the in vivo measurement of the β3-subunit and α7-subunit for the future, with further radiotracer development.”

In the paper

“Notably, the β2-subunit has been linked primarily to the reinforcing effects of nicotine22, 83, 84 and combines with the α3-6 subunits.”

What the sources say

• ?Not checked — no full text of the sourcecites [22] Picciotto M, Zoli M, Rimondin R, et al. Acetycholine receptors containing the beta2 subunit are involved in the reinforcing properties of nicotine. Nature. 1998;391:173–177. doi: 10.1038/34413. [DOI] [PubMed] [Google Scholar] source
• ?Not checked — no full text of the sourcecites [83] Walters CL, Brown S, Changeux JP, Martin B, Damaj MI. The beta2 but not alpha7 subunit of the nicotinic acetylcholine receptor is required for nicotine-conditioned place preference in mice. Psychopharmacology (Berl) 2006;184:339–44. doi: 10.1007/s00213-005-0295-x. [DOI] [PubMed] [Google Scholar] source
• ?Not checked — no full text of the sourcecites [84] Brunzell DH, Chang JR, Schneider B, Olausson P, Taylor JR, Picciotto MR. beta2-Subunit-containing nicotinic acetylcholine receptors are involved in nicotine-induced increases in conditioned reinforcement but not progressive ratio responding for food in C57BL/6 mice. Psychopharmacology (Berl) 2006;184:328–38. doi: 10.1007/s00213-005-0099-z. [DOI] [PubMed] [Google Scholar] source

In the paper

“In general, this may be due to differences in methodology or the higher relative dose of nicotine in the postmortem and animal studies.”