Nicotine In Cigarette Smoke Research Articles

Direct Extraction and Determination of Free Nicotine in Cigarette Smoke.

The accurate determination of the free nicotine content in cigarette smoke is crucial for assessing cigarette quality, studying harm and addiction, and reducing tar levels. Currently, the determination of free nicotine in tobacco products primarily relies on methods such as pH calculation, nuclear magnetic resonance (NMR) spectroscopy, headspace solid-phase microextraction (HS-SPME), and traditional solvent extraction. However, these methods have limitations that restrict their widespread application. In this study, the free nicotine in cigarette smoke was directly extracted by using cyclohexane according to the traditional solvent extraction method and detected via gas chromatography-mass spectrometry. Compared with the traditional two-phase solvent extraction, our experimental method is easy to execute and eliminates the influence of aqueous solutions on the original distribution of nicotine in cigarette smoke particulate matter. Furthermore, the presence of protonated nicotine in tobacco does not affect the determination. Compared with HS-SPME and NMR spectroscopy, our approach, which involves solvent extraction followed by chromatographic separation and instrumental detection, offers simplicity, improved precision, better detection limits, and reduced interference during the instrumental detection stage. The standard addition recoveries in the conducted experiment ranged from 96.2% to 102.5%. The limit of detection was 2.8 μg/cig, and the correlation coefficient (R2) for the quadratic regression of the standard curve exceeded 0.999. The relative standard deviation for parallel samples was between 1.7% and 3.4% (n = 5), fully meeting the requirements for the determination of free nicotine in cigarette smoke. Analysis of cigarette samples from 38 commercially available brands revealed that the content of free nicotine ranged from 0.376 to 0.716 mg/cig, with an average of 0.540 mg/cig, and free nicotine accounted for 39.1%-88.8% of the total nicotine content.

Investigation of exposure biomarkers in human plasma following differing levels of tobacco-specific N-nitrosamines and nicotine in cigarette smoke

Tobacco-specific N-nitrosamines (TSNAs) are strong carcinogens widely found in tobacco products, environmental tobacco smoke, lake, and wastewater. The main objective of this study was to investigate the effects of cigarette smoke with different yields of TSNAs (NNK, NNN, NAT, NAB) and nicotine on the levels of biomarkers of exposure in smokers’ plasma. Three hundred healthy volunteers were recruited comprising 60 smokers of each of 3 mg, 8 mg and 10 mg ISO tar yield cigarettes and 60 smokers who smoked 10 mg, 8 mg, and 3 mg for 14 days sequentially and 60 non-smokers. All study participants were male, aged from 21 to 45 years old, and were recruited from a same unit in Hebei, China. We measured the levels of NNAL, NAT, NNN, NAB and cotinine in plasma from 240 smokers and 60 non-smokers using a novel method established by online two-dimensional solid phase extraction-liquid chromatography-tandem mass spectrometry. The results showed that NNAL, NAT, NNN, NAB and cotinine in the plasma of smokers smoking cigarette with low TSNAs and nicotine were lower than that with high TSNAs and nicotine. When smokers switched from higher to lower TSNA yields of cigarettes, their plasma NNAL, NAT, NNN, NAB levels significantly decreased. The plasma concentrations of NNAL were significantly correlated with those of cotinine, NNN, NAT and NAB for smokers (p < 0.001). Similarly, the plasma concentrations of cotinine were significantly correlated with those of NNN, NAT and NAB for smokers (p < 0.001). The plasma NNAL, NAT, NNN, NAB and cotinine levels for smokers were significantly higher than those for non-smokers. These findings suggested that the total NNAL, NNN, NAT, NAB and cotinine in plasma were valid and reliable biomarkers for human exposure to TSNAs and nicotine.

Smoking and Fibrocystic Changes in the Breast: A Case Report of a Lifelong Smoker and Changes in Breast Parenchyma

Smoking is a well-known risk factor for breast cancer, and the nicotine in cigarette smoke has been associated with fibrotic changes in the breast. Although considered benign, these changes have the potential to make surgical dissection more difficult and may increase the risk of surgical complications. Here we discuss the case of a middle-aged female who was a lifelong smoker with breast cancer and who underwent a simple mastectomy. Intra-operatively, the overall breast parenchyma appeared quite firm, making tissue dissection challenging and the operating surgeon had to endure to remove the tumor and the remaining breast tissue.

Hypertension Prevention Education Through Training in Making Herbal Teas in Talango Village, Talango District, Sumenep Regency

Talango Village is one of the villages located in Talango District, Sumenep Regency. The people of this village make a living mainly as fishermen and farmers. One of the habits carried out by fishers and farmers in between their activities is smoking. The nicotine in cigarette smoke can increase blood pressure and heart rate, narrow arteries, harden their walls, and make blood more likely to clot. This condition can increase the risk of hypertension or high blood pressure. Based on interviews and surveys with partners Yayasan Jala Tani Pertiwi, education about hypertension prevention needs to be carried out to prevent hypertension in fishers and hypertension in Talango Village. This problem has prompted a service team to design educational activities to prevent hypertension by manufacturing herbal teas. This activity is structured through the first step, namely the preparation stage (compilation of training modules, participant selection, and evaluation media creation), the second stage (the process of implementing activities with pre-/post-test and discussion), and the third stage (evaluating the results of the training). A total of 20 farmers and fishers who are members of the Jala Tani Pertiwi Foundation were given education about hypertension, then continued with training to make anti-hypertensive herbal teas. The evaluation results showed an increase in participants' understanding of the material provided by 34%. Participants are known to have been able to understand and make herbal teas made from Moringa leaves, jasmine flowers, lemongrass leaves, and roselle flowers. Furthermore, to increase the participants' interest in this activity, the service team also taught them how to make tea packaging and how to sell it.

Assessing the effect of nicotine dose in cigarette smoking on sleep quality.

While several studies assessed the relation between cigarette smoking and sleep, there are still very few studies assessing the effect of nicotine in cigarette smoking on sleep. This study aimed to compare higher vs lower nicotine levels in cigarette smoking on sleep quality. We used data from the recently released dataset for the Randomized Trial of Reduced-Nicotine Standards for Cigarettes. We included three groups in the current study: the least nicotine concentration (i.e., 0.4 mg/g), a moderate nicotine concentration (i.e., 5.2 mg/g), and the highest nicotine concentration (i.e., 15.8 mg/g). For each participant, we included data regarding baseline and the last follow up at 6 weeks, where we compared insomnia, sleep problems, and awakening at night, in addition to different depression and affect scores. A total of 360 patients were included in this study, with a mean age of 42.4 (±13.4) years. For the three nicotine groups (i.e., 0.4 mg/g, 5.2 mg/g, and 15.8 mg/g), we included 119 (33%), 122 (34%), and 119 (33%) participants. Among the high-nicotine-dose group, the number of participants who had worsened sleep was significantly higher than the number of those who had improved sleep (p = 0.01) after 6 weeks of consumption, where 37 (31%) had worsened sleep score after 6 weeks while only 19 (16%) had improved score compared with baseline. While previous studies established a relation either between cigarette smoking and sleep or between nicotine patches and sleep, the present study is the first to establish that higher nicotine doses in cigarettes were associated with more sleep disturbances.

The Possible Effect of β -carotene on Nicotine Withdrawal in Testicular Tissue of Adult Male Albino Rats. Histological and Immunohistochemical Study.

AbstractBackground and Objectives: Nicotine in cigarette smoking possesses damaging effect on testis. This study was designed to evaluate and compare the prophylactic and therapeutic effects of β carotene on nicotine induced testicular damage during nicotine withdrawal.Materials and Methods:Thirty-nine adult male albino rats were used, 9 rats were control (GI), the remaining rats divided equally into 5 groups: GII (β carotene), GIII (Nicotine), GIV(Nicotine withdrawal), GV (Nicotine withdrawal therapeutic), GVI (Nicotine withdrawal prophylactic group). β carotene (10mg/kg/day) was injected intraperitoneally for 4 weeks. Nicotine (4 mg/kg/day) was injected intraperitoneally for 4 weeks. Before sacrifaction, blood samples were drawn to assess serum levels of malondialdehyde (MDA) and testosterone. After sacrifaction, testicular sections were stained with H&E, Masson trichrome (to reveal collagen fiber deposition and distribution) and immunohistochemically for Vimentin (Sertoli cell intermediate filament(. Morphometric measurements were done by computerized image analysis.Results:Groups I and II showed similar results with normal testicular histological architecture, biochemical and morphometrical results. Deterioration of histological architecture, biochemical and morphometric parameters were recorded in groups III, IV and V (mostly GIII) with significant decrease in diameter of seminiferous tubules, height of spermatogenic epithelium, area percent of vimentin reaction and significant increase in area percent of collagen fibres deposition compared to GI. GVI showed better results than GIII, GIV and GV with restoration of normal testicular histological structure.Conclusion: β carotene could help in improving spermatogenesis. Administration of β carotene prophylactically during nicotine exposure and withdrawal gives better histological, biochemical and morphometrical results than therapeutic administration during nicotine withdrawal period only.

Divergent Effect of Cigarette Smoke on Innate Immunity in Inflammatory Bowel Disease: A Nicotine-Infection Interaction.

Cigarette smoke (CS) has adverse effects in patients with Crohn’s disease (CD), an inflammatory bowel disease (IBD) that has been associated with microbial infection, immuno-dysregulation, and mucosal dysfunction. However, CS seems to provide relief and protection to patients with another IBD known as ulcerative colitis (UC). These two subsets are featured as M1- and M2-mediated responses, respectively. Nicotine is the most active, addictive, and studied ingredient in CS. The mechanism of how nicotine and/or other CS ingredients induce pro-inflammatory or anti-inflammatory phenotypes in IBD patients remains under investigation. Our most recent in vitro nicotine study provided significant insights toward understanding the contradictory effects of nicotine on IBD patients, and it elucidated the mechanistic role of α7nAChR in modulation of macrophages in tobacco smokers. Shifting the beneficial effect of nicotine to a harmful outcome in CD patients was linked to a nicotine-microbe interaction that supports a microbial etiology in CD pathogenesis. Among the most debated pathogens in CD etiology is Mycobacterium avium subspecies paratuberculosis (MAP). Other studies associated nicotine with upregulation of miR-124 expression in macrophages, which led to anti-inflammatory response. This review discusses published work on the role of nicotine in modulation of the innate immune response and subsequent signaling in macrophages in IBD subsets.

Abstract P390: Comparison of the Acute Autonomic Effects of Mainstream Cigarette Smoke to Oral Nicotine Spray

Background: Smoking and exposure to environmental tobacco smoke are associated with sympathetic nervous system activation, a leading putative mechanism of adverse cardiovascular events. However, the role of nicotine in cigarette smoke’s sympathomimetic effects remains unknown. Methods: Healthy young smokers were recruited and fasted from food and nicotine/tobacco products for ≥8 hours before each of two visits. On each visit, participants underwent a 12-lead resting electrocardiogram (ECG) for 5 minutes indoors (pre-exposure), 20 minutes outdoors (mid-exposure), and 5 minutes indoors (post-exposure). On the first day, participants smoked cigarette of their preferred brand, and on second day used 4 mg of oral nicotine spray instead. We present preliminary heart rate variability results from 10 smokers who completed two visits (mean age 28 years, 7 males, 0.8 -1.2 mg nicotine per cigarette). Results: Heart rate (HR) increased from 65 ± 20 beats/min (BPM) at pre-exposure to 80 ± 25 BPM during cigarette use (23% increase), and to 78 ± 37 BPM during use of nicotine alone (20% increase) (p&lt;0.05 vs pre-exposure). There was no significant difference in average HR between pre and post exposure. SDRR did not change significantly between phases and exposures (Pre, mid and post exposure (ms) for cigarette; 59 ± 20, 68 ± 25, 57 ± 20 and for nicotine; 70 ± 26, 79 ± 37 and 62 ± 22, respectively.) However, RMSSD decreased with cigarette use by 25% (p&lt;0.01), and also with nicotine but was not significant. Conversely, LF/HF increased during cigarette and nicotine-only exposures relative to pre- (&gt;150%) and post-exposure (&gt;15%) (p&lt;0.05). Conclusion: Our findings suggest smoking may acutely induce relative sympathetic dominance through nicotine, with potential additive effects of other aerosol constituents within tobacco smoke (e.g., aldehydes and particulates).

Lung eosinophilia induced by house dust mites or ovalbumin is modulated by nicotinic receptor α7 and inhibited by cigarette smoke.

Eosinophilia (EOS) is an important component of airway inflammation and hyperresponsiveness in allergic reactions including those leading to asthma. Although cigarette smoking (CS) is a significant contributor to long-term adverse outcomes in these lung disorders, there are also the curious reports of its ability to produce acute suppression of inflammatory responses including EOS through poorly understood mechanisms. One possibility is that proinflammatory processes are suppressed by nicotine in CS acting through nicotinic receptor α7 (α7). Here we addressed the role of α7 in modulating EOS with two mouse models of an allergic response: house dust mites (HDM; Dermatophagoides sp.) and ovalbumin (OVA). The influence of α7 on EOS was experimentally resolved in wild-type mice or in mice in which a point mutation of the α7 receptor (α7E260A:G) selectively restricts normal signaling of cellular responses. RNA analysis of alveolar macrophages and the distal lung epithelium indicates that normal α7 function robustly impacts gene expression in the epithelium to HDM and OVA but to different degrees. Notable was allergen-specific α7 modulation of Ccl11 and Ccl24 (eotaxins) expression, which was enhanced in HDM but suppressed in OVA EOS. CS suppressed EOS induced by both OVA and HDM, as well as the inflammatory genes involved, regardless of α7 genotype. These results suggest that EOS in response to HDM or OVA is through signaling pathways that are modulated in a cell-specific manner by α7 and are distinct from CS suppression.

Nicotine Impairs Macrophage Control of Mycobacterium tuberculosis.

Pure nicotine impairs macrophage killing of Mycobacterium tuberculosis (MTB), but it is not known whether the nicotine component in cigarette smoke (CS) plays a role. Moreover, the mechanisms by which nicotine impairs macrophage immunity against MTB have not been explored. To neutralize the effects of nicotine in CS extract, we used a competitive inhibitor to the nicotinic acetylcholine receptor (nAChR)-mecamylamine-as well as macrophages derived from mice with genetic disruption of specific subunits of nAChR. We also determined whether nicotine impaired macrophage autophagy and whether nicotine-exposed T regulatory cells (Tregs) could subvert macrophage anti-MTB immunity. Mecamylamine reduced the CS extract increase in MTB burden by 43%. CS extract increase in MTB was also significantly attenuated in macrophages from mice with genetic disruption of either the α7, β2, or β4 subunit of nAChR. Nicotine inhibited autophagosome formation in MTB-infected THP-1 cells and primary murine alveolar macrophages, as well as increased the intracellular MTB burden. Nicotine increased migration of THP-1 cells, consistent with the increased number of macrophages found in the lungs of smokers. Nicotine induced Tregs to produce transforming growth factor-β. Naive mouse macrophages co-cultured with nicotine-exposed Tregs had significantly greater numbers of viable MTB recovered with increased IL-10 production and urea production, but no difference in secreted nitric oxide as compared with macrophages cocultured with unexposed Tregs. We conclude that nicotine in CS plays an important role in subverting macrophage control of MTB infection.

Hazards of nicotine on the uterus of albino rat and the possible ameliorative role of human chorionic gonadotropin (hCG)

Introductions: Smoking is an important cause of increased mortality and morbidity in the developing countries. Nicotine in cigarette smoke is one of the toxic substances which impair the fertility.So, the aim of this work was to study the histological changes induced by nicotine hydrogen tartrate on the endometrium of albino rat and the possible ameliorative effect of human chorionic gonadotropin (hCG).Material and Methods: Forty females of Wister albino rats in the normal estrous cycle were selected and used for the experiment. The experimental animals were randomly divided into four groups, each one including 10 female rats. The experiment period was extended to four weeks.Group I was (control group). Group II (Nicotine treated group) was subcutaneously (SC) injected by nicotine hydrogen tartrate as 8 mg/rat three times/week for four weeks. Group III (Nicotine and hCG) was subcutaneously injected with the previous dose of nicotine together with hCG (pregnyl). HCG was subcutaneously injected as 2 IU/rat/day for four weeks. Group IV (hCG group) was subcutaneously injected only with hCG as 2.0 IU/rat/day for four weeks. The specimens were prepared for light and scanning electron microscopic examinations, and morphometric measurements.Results: Nicotine induced decrease in the thickness of the endometrium. The height of the surface epithelium was decreased, the endometrial stromal cells were disrupted and had congested blood vessels. The endometrial glands became small and atrophied. The endometrium showed apparent increase in collagen fibers, a weak PAS reaction and highly positive immunohistochemical staining KI 67. Scanning electron microscopic examination revealed flattening of the surface epithelial cells with absent apical microvilli and apparent decrease in the number of pits of the glands. Concomitant administration of nicotine and hCG showed marked improvement in the structures of the endometrium as compared with that of the nicotine-treated group.Conclusion: Nicotine altered the structure of the endometrium and concomitant administration of hCG with nicotine improved it.

Nicotine and cigarette smoke modulate Nrf2-BDNF-dopaminergic signal and neurobehavioral disorders in adult rat cerebral cortex.

Nicotine and cigarette smoking (CS) are associated with addiction behavior, drug-seeking, and abuse. However, the mechanisms that mediate this association especially, the role of brain-derived neurotrophic factor (BDNF), dopamine (DA), and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling in the cerebral cortex, are not fully known. Therefore, we hypothesized that overexpression of BDNF and DA, and suppression of Nrf2 contribute to several pathological and behavioral alterations in adult cerebral cortex. Methodology/Principal Observations: We treated Wistar rats with different doses of oral nicotine and passive CS for 4-week (short-term) and 12-week (long-term) duration, where doses closely mimic the human smoking scenario. Our result showed dose-dependent association of anxiogenic and depressive behavior, and cognitive interference with neurodegeneration and DNA damage in the cerebral cortex upon exposure to nicotine/CS as compared to the control. Further, the results are linked to upregulation of oxidative stress, overexpression of BDNF, DA, and DA marker, tyrosine hydroxylase (TH), with concomitant downregulation of ascorbate and Nrf2 expression in the exposed cerebral cortex when compared with the control. Overall, our data strongly suggest that the intervention of DA and BDNF, and depletion of antioxidants are important factors during nicotine/CS-induced cerebral cortex pathological changes leading to neurobehavioral impairments, which could underpin the novel therapeutic approaches targeted at tobacco smoking/nicotine's neuropsychological disorders including cognition and drug addiction.

Endothelial disruptive proinflammatory effects of nicotine and e-cigarette vapor exposures.

The increased use of inhaled nicotine via e-cigarettes has unknown risks to lung health. Having previously shown that cigarette smoke (CS) extract disrupts the lung microvasculature barrier function by endothelial cell activation and cytoskeletal rearrangement, we investigated the contribution of nicotine in CS or e-cigarettes (e-Cig) to lung endothelial injury. Primary lung microvascular endothelial cells were exposed to nicotine, e-Cig solution, or condensed e-Cig vapor (1-20 mM nicotine) or to nicotine-free CS extract or e-Cig solutions. Compared with nicotine-containing extract, nicotine free-CS extract (10-20%) caused significantly less endothelial permeability as measured with electric cell-substrate impedance sensing. Nicotine exposures triggered dose-dependent loss of endothelial barrier in cultured cell monolayers and rapidly increased lung inflammation and oxidative stress in mice. The endothelial barrier disruptive effects were associated with increased intracellular ceramides, p38 MAPK activation, and myosin light chain (MLC) phosphorylation, and was critically mediated by Rho-activated kinase via inhibition of MLC-phosphatase unit MYPT1. Although nicotine at sufficient concentrations to cause endothelial barrier loss did not trigger cell necrosis, it markedly inhibited cell proliferation. Augmentation of sphingosine-1-phosphate (S1P) signaling via S1P1 improved both endothelial cell proliferation and barrier function during nicotine exposures. Nicotine-independent effects of e-Cig solutions were noted, which may be attributable to acrolein, detected along with propylene glycol, glycerol, and nicotine by NMR, mass spectrometry, and gas chromatography, in both e-Cig solutions and vapor. These results suggest that soluble components of e-Cig, including nicotine, cause dose-dependent loss of lung endothelial barrier function, which is associated with oxidative stress and brisk inflammation.

Regulation of Cigarette Smoke Induction of IL-8 in Macrophages by AMP-activated Protein Kinase Signaling.

Inhaled cigarette smoke (CS) causes persistent lung inflammation in smokers. Interleukin 8 (IL-8) released from macrophages is a key chemokine during initiation and progression of CS-induced lung inflammation, yet its regulation is largely unknown. AMP-activated protein kinase (AMPK), a crucial energy homeostasis regulator, may modulate inflammation. Here we report that CS extract (CSE) increased the level of intracellular reactive oxygen species (ROS), activating AMPK, mitogen-activated protein kinases (MAPKs), and NF-κB, as well as inducing IL-8, in human macrophages. N-acetyl-cysteine (ROS scavenger) or hexamethonium [nicotinic acetylcholine receptor (nAChR) antagonist] attenuated the CSE-induced increase in intracellular ROS, activation of AMPK and NF-κB, as well as IL-8 induction, which suggests that nAChRs and ROS are important. Prevention of AMPK activation by compound C or AMPK siRNA reduced CSE-induced IL-8 production, confirming the role of AMPK. Compound C or AMPK siRNA also inhibited the activation of MAPKs and NF-κB by CSE, which suggests that these molecules are downstream of AMPK. Additionally, exposure of human macrophages to nicotine activated AMPK and induced IL-8 and that these effects were lessened by hexamethonium or compound C, implying that nicotine in CS may be causative. Furthermore, chronic CS exposure in mice promoted AMPK phosphorylation and expression of MIP-2 (an IL-8 homolog) in infiltrated macrophages and in lung tissues, as well as induced lung inflammation, all of which were reduced by compound C treatment. Thus, we identified a novel nAChRs-dependent, ROS-sensitive, AMPK/MAPKs/NF-κB signaling pathway, which seems to be important to CS-induced macrophage IL-8 production and possibly to lung inflammation.

Cigarette smoke causes RV dysfunction and cardiac fibroblast proliferation (1090.8)

Chronic obstructive pulmonary disease (COPD) is frequently associated with right ventricular (RV) dysfunction. Cigarette smoke (CS) is the leading cause of COPD. Male AKR mice subjected to CS for 6 weeks recapitulate the RV dysfunction seen in patients with COPD but without pulmonary hypertension (PH). Mice exposed to CS had reduced tricuspid annular plane systolic excursion (TAPSE) suggesting decreased RV function compared to mice exposed to room air (RA) (1.1±0.1 vs. 0.8±0.1, respectively, P&lt;0.05). Collagen content was increased in the RV of CS‐exposed mice, compared to RA (11.3±0.7 vs. 9.0±0.7, respectively, P&lt;0.05). In primary isolated cardiac fibroblasts (CF) exposed to 10% CS extract for 24 hours, proliferation was increased by ~2‐fold (normalized cell count of 1.97±0.15 vs. 1.0±0.0, respectively, P&lt;0.01). CF proliferation was unaffected by the inhibition of reactive oxygen species or aldehydes but was significantly reduced by mecamylamine, an inhibitor of nicotinic acetylcholine receptors (nAChR). Further, nicotine (200‐600nM) dose‐dependently increased CF proliferation. Additionally, exposure to CS extract or nicotine significantly increased PKCalpha expression in CF and increased expression of the activated form of the mitogen activated protein kinase, ERK1/2. These data suggest that nicotine in CS causes CF proliferation that may be mediated by nAChRs, PKCalpha and ERK signaling.

Not so Cool? Menthol’s discovered actions on the nicotinic receptor and its implications for nicotine addiction

Nicotine cigarette smoke is a large public health burden worldwide, contributing to various types of disease. Anti-tobacco media campaigns and control programs have significantly reduced smoking in the United States, yet trends for menthol cigarette smoking have not been as promising. Menthol cigarette smoking is particularly prevalent among young adults and African Americans, with implications for long-term impacts on health care. Continuing high rates of menthol cigarette addiction call into question the role of menthol in nicotine addiction. To date, a biological basis for the high rate of addiction and relapse among menthol cigarette smokers has not been defined. Studies have demonstrated a role for menthol in the metabolism of nicotine in the body. More recent findings now reveal an interaction between menthol and the nicotinic acetylcholine (nACh) receptor in cells. This receptor is central to the actions of nicotine in the brain, and plays an important role in nicotine addiction. The newly discovered effect of menthol on nACh receptors may begin to explain the unique addictive properties of menthol cigarettes.

Nicotine delivery to rats via lung alveolar region-targeted aerosol technology produces blood pharmacokinetics resembling human smoking.

Nicotine is a heavily used addictive drug acquired through smoking tobacco. Nicotine in cigarette smoke is deposited and absorbed in the lungs, which results in a rapidly peaked slowly declining arterial concentration. This pattern plays an important role in initiation of nicotine addiction. A method and device were developed for delivering nicotine to rodents with lung alveolar region-targeted aerosol technology. The dose of delivery can be controlled by the nicotine aerosol concentration and duration of exposure. Our data showed that, in the breathing zone of the nose-only exposure chamber, the aerosol droplet size distribution was within the respirable diameter range. Rats were exposed to nicotine aerosol for 2 min. The arterial blood nicotine concentration reached 43.2 ± 15.7 ng/ml (mean ± SD) within 1-4 min and declined over the next 20 min, closely resembling the magnitude and early pharmacokinetics of a human smoking a cigarette. The acute inhalation toxicity of nicotine: LC50 = 2.3mg/L was determined; it was affected by pH, suggesting that acidification decreases nicotine absorption and/or bioavailability. A noninvasive method and toolkit were developed for delivering nicotine to rodents that enable rapid delivery of a controllable amount of nicotine into the systemic circulation and brain-inducing dose-dependent pharmacological effects, even a lethal dose. Aerosol inhalation can produce nicotine kinetics in both arterial and venous blood resembling human smoking. This method can be applied to studies of the effects of chronic intermittent nicotine exposure, nicotine addiction, toxicology, tobacco-related diseases, teratogenicity, and for discovery of pharmacological therapeutics.

Impact of COMT Val 108/158 Met and DRD2 Taq1B Gene Polymorphisms on Vulnerability to Cigarette Smoking of Thai Males

The nicotine in cigarette smoke can stimulate the dopaminergic reward pathways. The catechol O-methyltransferase gene (COMT) and dopamine receptor 2 gene (DRD2) are dopamine-related genes. Genetic polymorphisms in these two genes are potential candidates in determining an individual's predisposition to cigarette smoking. The purposes of this study were to examine the association between two polymorphisms in COMT Val (108/158) Met and DRD2 Taq1B and anthropometric-biochemical parameters and to ascertain the association between these polymorphisms and cigarette smoking. The levels of anthropometric-biochemical parameters were determined. COMT Val (108/158) Met and DRD2 Taq1B polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism technique. With regard to COMT Val (108/158) Met and DRD2 Taq1B polymorphisms, no differences were found in anthropometric-biochemical variables, except for thiocyanate concentration. Smoking status was significantly associated with COMT Val (108/158) Met polymorphism, but not associated with DRD2 Taq1B polymorphism. Logistic regression analysis showed that COMT Val (108/158) Met gene polymorphism, educational status, parental smoking, and alcohol consumption had statistically significant impacts on cigarette smoking. The results suggest that COMT Val (108/158) Met genetic polymorphisms, but not DRD2 Taq1B, may influence susceptibility to cigarette smoking among Thai males.

Denicotinized Versus Average Nicotine Tobacco Cigarette Smoking Differentially Releases Striatal Dopamine

Nicotine has long been recognized as a necessary but insufficient component of tobacco cigarettes to maintain a psychophysiological need to smoke. This study examined venous plasma concentrations effects of nicotine in cigarette smoking after overnight abstinence to release striatal dopamine (DA). Twenty-two male smokers smoked either denicotinized (denic) or average nicotine (nic) cigarettes under single blind conditions. Each was given [(11)C]raclopride and scanned in a positron emission tomography (PET) facility. Smoking either denic or nic cigarettes released striatal DA. Denic cigarette smoking released DA primarily in the right striatum, whereas nic cigarette smoking released DA in both striata, but especially in the left. Increases in venous plasma nicotine concentrations correlated positively with increased DA release in the left caudate nucleus. Smoking denic cigarettes reduced craving as much as smoking nic cigarettes. Craving reduction after nic tobacco smoking correlated with increases in plasma nicotine. Nonnicotine factors in tobacco smoking produce important right brain effects. Nicotine is a pharmacological factor during tobacco smoking that releases bilateral striatal DA, but more in the left brain.

Rapid Effect of Nicotine Intake on Neuroplasticity in Non-Smoking Humans

In various studies nicotine has shown to alter cognitive functions in non-smoking subjects. The physiological basis for these effects might be nicotine-generated modulation of cortical structure, excitability, and activity, as mainly described in animal experiments. In accordance, a recently conducted study demonstrated that application of nicotine for hours via nicotine patch in non-smoking humans alters the effects of neuroplasticity-inducing non-invasive brain stimulation techniques on cortical excitability. Specifically, nicotine abolished inhibitory plasticity independent from the focality of the stimulation protocol. While nicotine prevented also the establishment of non-focal facilitatory plasticity, focal synapse-specific facilitatory plasticity was enhanced. These results agree with a focusing effect of prolonged nicotine application on facilitatory plasticity. However, since nicotine induces rapid adaption processes of its receptors, this scenario might differ from the effect of nicotine in cigarette smoking. Thus in this study we aimed to gain further insight in the mechanism of nicotine on plasticity by exploring the effect of nicotine spray on non-focal and focal plasticity-inducing protocols in non-smoking subjects, a fast-acting agent better comparable to cigarette smoking. Focal, synapse-specific plasticity was induced by paired associative stimulation (PAS), while non-focal plasticity was elicited by transcranial direct current stimulation (tDCS). Forty eight non-smokers received nicotine spray respectively placebo combined with one of the following protocols (anodal tDCS, cathodal tDCS, PAS-25, and PAS-10). Corticospinal excitability was monitored via motor-evoked potentials elicited by transcranial magnetic stimulation (TMS). Nicotine spray abolished facilitatory plasticity irrespective of focality and PAS-10-induced excitability diminution, while tDCS-derived excitability reduction was delayed and weakened. Nicotine spray had thus a clear effect on neuroplasticity in non-smoking subjects. However, the effects of nicotine spray differ clearly from those of prolonged nicotine application, which might be due to missing adaptive nicotinic receptor alterations. These results enhance our knowledge about the dynamic impact of nicotine on plasticity, which might be related to its heterogenous effect on cognition.