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Sample records for 4-mg nicotine lozenge

  1. Nicotine Lozenges

    MedlinePlus

    ... is stopped and to reduce the urge to smoke. ... often than prescribed by your doctor.If you smoke your first cigarette within 30 minutes of waking ... should use 4-mg nicotine lozenges. If you smoke your first cigarette more than 30 minutes after ...

  2. Comparative Effectiveness of the Nicotine Lozenge and Tobacco-Free Snuff for Smokeless Tobacco Reduction

    PubMed Central

    Ebbert, Jon O.; Severson, Herbert H.; Croghan, Ivana T.; Danaher, Brian G.; Schroeder, Darrell R.

    2013-01-01

    Long-term smokeless tobacco (ST) use is associated with cardiovascular disease and cancer, but not all ST users want to quit. Previous studies have evaluated the effectiveness of nicotine lozenges and tobacco-free snuff for reducing ST use among ST users not ready to quit, but no comparative effectiveness trials of these two products have been conducted. We conducted a multicenter, randomized clinical pilot study evaluating the comparative effectiveness of the 4-mg nicotine lozenge and tobacco-free snuff for reducing ST use and increasing tobacco abstinence among ST users with no intention of quitting in the next 30 days. Participants received 8 weeks of treatment and behavioral counseling on tobacco reduction strategies with follow-up to 26 weeks. We randomized 81 participants (40 nicotine lozenges, 41 tobacco-free snuff). No significant differences in reduction were observed between the two groups at weeks 8, 12, and 26. No signficant differences were observed between groups in nicotine withdrawal or tobacco craving. However, both groups significantly reduced (p < .001) ST use in cans/week and dips/day from baseline which was sustained through the end-of-study. The observed biochemically-confirmed abstinence rates at week 26 were similar between groups (12% vs. 12%, one-tailed p = .615). The 4-mg nicotine lozenge and the tobacco-free snuff both appear to be effective and comparable for reducing ST use among ST users not ready to quit in the next 30 days. PMID:23454876

  3. Nicotine replacement therapy

    MedlinePlus

    ... come in many forms: Gum Inhalers Lozenges Nasal spray Skin patch All of these work well if ... inhaler and patch together when quitting. Nicotine Nasal Spray The nasal spray provides a quick dose of ...

  4. The influence of acutely administered nicotine on cue-induced craving for gambling in at-risk video lottery terminal gamblers who smoke.

    PubMed

    McGrath, Daniel S; Dorbeck, Anders; Barrett, Sean P

    2013-04-01

    Evidence indicates that tobacco use and gambling often co-occur. Despite this association, little is known about how tobacco use affects the propensity to gamble. Nicotine, the putative addictive component of tobacco, has been reported to potentiate the hedonic value of other nonsmoking stimuli. Environmental cues have been identified as an important contributor to relapse in addictive behavior; however, the extent to which nicotine can affect the strength of gambling cues remains unknown. This study examined whether nicotine influences subjective ratings for gambling following gambling cues. In a mixed within/between-subjects design, 30 (20 men) video lottery terminal (VLT) gamblers ('moderate-risk' or 'problem' gamblers) who smoke daily were assigned to nicotine (4 mg deliverable) or placebo lozenge conditions. Subjective and behavioral responses were assessed at baseline, following lozenge, following neutral cues, and following presentation of gambling cues. Nicotine lozenge was found to significantly reduce tobacco-related cravings (P<0.05) but did not affect gambling-related cravings, the choice to play a VLT, or other subjective responses. These results suggest that a low dose of acutely administered nicotine does not increase cue-induced craving for gambling in at-risk VLT gamblers who smoke. PMID:23412113

  5. Lozenge Tilings and Hurwitz Numbers

    NASA Astrophysics Data System (ADS)

    Novak, Jonathan

    2015-10-01

    We give a new proof of the fact that, near a turning point of the frozen boundary, the vertical tiles in a uniformly random lozenge tiling of a large sawtooth domain are distributed like the eigenvalues of a GUE random matrix. Our argument uses none of the standard tools of integrable probability. In their place, it uses a combinatorial interpretation of the Harish-Chandra/Itzykson-Zuber integral as a generating function for desymmetrized Hurwitz numbers.

  6. New Product Marketing Blurs the Line Between Nicotine Replacement Therapy and Smokeless Tobacco Products.

    PubMed

    Kostygina, Ganna; England, Lucinda; Ling, Pamela

    2016-07-01

    Tobacco companies have begun to acquire pharmaceutical subsidiaries and recently started to market nicotine replacement therapies, such as Zonnic nicotine gum, in convenience stores. Conversely, tobacco companies are producing tobacco products such as tobacco chewing gum and lozenges that resemble pharmaceutical nicotine replacement products, including a nicotine pouch product that resembles snus pouches. This convergence of nicotine and tobacco product marketing has implications for regulation and tobacco cessation. PMID:27077338

  7. Nicotine Replacement Therapy: An Overview

    PubMed Central

    Wadgave, Umesh; Nagesh, L

    2016-01-01

    Today tobacco use is the single greatest preventable cause of death in the world. Tobacco use is often incorrectly perceived to be solely a personal choice. This is contradicted by the fact that when fully aware of the health impact, most tobacco users want to quit but find it difficult to stop due to the addictiveness of nicotine. Henceforth, Nicotine replacement therapy (NRT) came into existence which temporarily replaces much of the nicotine from tobacco to reduce motivation to consume tobacco and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence. Various alternative nicotine sources (gum, transdermal patch, nasal spray, inhaler and sublingual tablets/lozenges) have been incorporated into tobacco cessation programs. Recent research is more focusing on rapid delivery of nicotine (Nicotine preloading, true pulmonary inhaler) and immunological approaches (nicotine vaccine) to tackle nicotine dependence. These NRTs are in general well tolerated and have minimal adverse effects. The review aims to summarize literature on various modes of nicotine replacement therapy methods currently used to treat nicotine dependence, and to give an overview about future possible approaches to treat tobacco use disorder. PMID:27610066

  8. Nicotine Replacement Therapy: An Overview.

    PubMed

    Wadgave, Umesh; Nagesh, L

    2016-07-01

    Today tobacco use is the single greatest preventable cause of death in the world. Tobacco use is often incorrectly perceived to be solely a personal choice. This is contradicted by the fact that when fully aware of the health impact, most tobacco users want to quit but find it difficult to stop due to the addictiveness of nicotine. Henceforth, Nicotine replacement therapy (NRT) came into existence which temporarily replaces much of the nicotine from tobacco to reduce motivation to consume tobacco and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence. Various alternative nicotine sources (gum, transdermal patch, nasal spray, inhaler and sublingual tablets/lozenges) have been incorporated into tobacco cessation programs. Recent research is more focusing on rapid delivery of nicotine (Nicotine preloading, true pulmonary inhaler) and immunological approaches (nicotine vaccine) to tackle nicotine dependence. These NRTs are in general well tolerated and have minimal adverse effects. The review aims to summarize literature on various modes of nicotine replacement therapy methods currently used to treat nicotine dependence, and to give an overview about future possible approaches to treat tobacco use disorder. PMID:27610066

  9. The future of nicotine replacement.

    PubMed

    Russell, M A

    1991-05-01

    Following in the wake of progress forged by nicotine chewing gum, a new generation of nicotine replacement products will soon be available as aids to giving up smoking. These range from nicotine skin patches, which take 6-8 hrs to give very flat steady-state peak blood levels, to nicotine vapour inhalers which mimic the transient high-nicotine boli that follow within a few seconds of each inhaled puff of cigarette smoke. Other products undergoing clinical trials include a nasal nicotine spray and nicotine lozenges. It is argued here that it is not so much the efficacy of new nicotine delivery systems as temporary aids to cessation, but their potential as long-term alternatives to tobacco that makes the virtual elimination of tobacco a realistic future target. Their relative safety compared with tobacco is discussed. A case is advanced for selected nicotine replacement products to be made as palatable and acceptable as possible and actively promoted on the open market to enable them to compete with tobacco products. They will also need health authority endorsement, tax advantages and support from the anti-smoking movement if tobacco use is to be gradually phased out altogether. PMID:1859935

  10. Zinc ion availability--the determinant of efficacy in zinc lozenge treatment of common colds.

    PubMed

    Eby, G A

    1997-10-01

    This is a re-analysis of reports from 1984 to 1992 of double-blind, placebo-controlled, clinical trials of zinc lozenges in the treatment of common colds. This re-analysis was performed to test the hypothesis that major variations in daily zinc ion availability (ZIA) between chemically different lozenge formulations caused differing results in these clinical trials. Solution chemistry computations determined the bioavailability of Zn2+ ions at physiological pH from the lozenges used in these clinical trails. ZIA was derived from Fick's laws of diffusion in a bio-electric field. Lozenges that released Zn2+ ions at physiological pH (positive ZIAs) shortened colds. Lozenges that released negatively charged zinc species at physiological pH (negative ZIAs) lengthened colds. Lozenges having a zero ZIA had no effect on common colds. Lozenges with ZIA = 100 shortened colds by 7 days while ZIA = -55 lozenges lengthened colds by 4.4 days. A linear dose-response relationship exists between ZIAs of zinc lozenges and changes in duration of common colds. It is concluded that: prospective efficacy of zinc lozenges can be predicted based upon readily determined ZIA factors and ZIAs; chemically different zinc lozenge formulations having greatly different ZIAs resulted in greatly differing results in clinical trials; mast cell granule-derived Zn2+ ions are the foundation of the primary immune system; and high ZIA zinc acetate lozenges are beneficial for common colds. PMID:9372416

  11. Bioadhesive lozenge for the improved delivery of cetylpyridinium chloride.

    PubMed

    Collins, A E; Deasy, P B

    1990-02-01

    Conventional lozenges produce a high initial release of drug in the oral cavity, which rapidly declines to subtherapeutic levels, and requires multiple daily administration with associated problems of systemic toxicity and compliance. Various multilayer compacts containing cetylpyridinium chloride were evaluated in vitro using release into simulated saliva (buffer pH 6.6). The drug loading, the wax content of the active layer, and the composition of the bioadhesive layer were important variables affecting product performance. Following preliminary in vivo studies, the release of a three-layered device containing drug in a nonadhesive and flavored waxy exposed layer was studied in six humans using HPLC and was shown not to be affected by location within the mouth. In comparison with a proprietary lozenge formulation, the device produced more uniform and effective levels of drug (approximately 20 micrograms.mL-1), with adequate comfort, taste, and irritancy over a period of 3 h. PMID:2324958

  12. Efficacy of Ambroxol lozenges for pharyngitis: a meta-analysis

    PubMed Central

    2014-01-01

    Background Ambroxol has a local anaesthetic action and is marketed for pain relief for sore throat. The objective is to examine the efficacy and safety of ambroxol for the relief of pain associated with acute uncomplicated sore throat. Methods A systematic review of the literature and meta-analysis. Selection criteria consisted of randomized controlled trials which compared ambroxol to placebo or any other treatment for sore throat. Two reviewers independently assessed for relevance, inclusion, and risk of bias. Weighted mean differences (WMDs) were calculated and are reported with corresponding 95% confidence intervals (CIs). Results and conclusion From 14 potentially relevant citations, five trials reported in three publications met the inclusion criteria, three of them were published twice. Ambroxol lozenges were compared in different dosages (5–30 mg) with mint flavoured lozenges and once with benzocaine. Main outcome was a ratio of pain reduction measured repeatedly over 3 h compared to baseline on 6-item verbal rating scale. A total of 1.772 adult patients participated in the trials. Pain intensity decreased in both study arms. A meta-analysis of the 5 controlled trials resulted in a difference in pain reduction compared to placebo of -0.11 (95% CI [-0.15, -0.07]; p < 0.0001) favouring ambroxol 20 mg. Quality of reporting of the studies was low. Ambroxol is slightly more effective in relieving pain in acute sore throat than mint flavoured lozenges over a period of 3 h. However, the additional benefits of ambroxol beyond three hours, remain unclear given that more than 50% of patients using mint flavoured lozenges for pain relief reported good or very good efficacy after 1 day compared to 69% with ambroxol. Ambroxol is a safe option for individual patients with mainly local symptoms asking for treatment. PMID:24621446

  13. Zinc lozenges: cold cure or candy? Solution chemistry determinations.

    PubMed

    Eby, George A

    2004-02-01

    Common colds were shortened by 7 days in a 1984 clinical trial using zinc gluconate throat lozenges each 2 h. Between then and 2004, 10 other double-blind, placebo-controlled clinical trials showed widely varying results. This re-analysis of these trials presents solution chemistry methods to elucidate differences in efficacy. Statistically significant correlation was shown between total daily dosages of positively charged zinc species and reductions in median (p = 0.005) and mean duration (p < 0.02) of common colds in these trials. PMID:15499830

  14. The fentanyl 'lozenge' story: from books to battlefield.

    PubMed

    Aldington, Dominic; Jagdish, S

    2014-06-01

    This article outlines the process that led to the introduction of the fentanyl lozenge for acute pain management. It starts with the historical context before discussing the recognition of an ongoing problem and then identifies the options that were considered. There follows a description of the pharmacology of fentanyl before describing the trial of concept that was conducted. This leads into an outline of the meetings and committees that had to be engaged with before the final acceptance and subsequent ushering in. The final section describes an option that was unsuccessful. PMID:24413475

  15. Differential discriminative-stimulus effects of cigarette smoke condensate and nicotine in nicotine-discriminating rats.

    PubMed

    Lee, Jun-Yeob; Choi, Mee Jung; Choe, Eun Sang; Lee, Young-Ju; Seo, Joung-Wook; Yoon, Seong Shoon

    2016-06-01

    Although it is widely accepted that nicotine plays a key role in tobacco dependence, nicotine alone cannot account for all of the pharmacological effects associated with cigarette smoke found in preclinical models. Thus, the present study aimed to determine the differential effects of the interoceptive cues of nicotine alone versus those of cigarette smoke condensate (CSC) in nicotine-trained rats. First, the rats were trained to discriminate nicotine (0.4mg/kg, subcutaneous [s.c.]) from saline in a two-lever drug discrimination paradigm. Then, to clarify the different neuropharmacological mechanisms underlying the discriminative-stimulus effects in the nicotine and CSC in nicotine-trained rats, either the α4β2 nicotinic acetylcholine receptor (nAChR) antagonist dihydro-β-erythroidine (DHβE; 0.3-1.0mg/kg, s.c.) or the α7 nAChR antagonist methyllycaconitine citrate (MLA; 5-10mg/kg, intraperitoneal [i.p.]) was administered prior to the injection of either nicotine or CSC. Separate set of experiments was performed to compare the duration of action of the discriminative-stimulus effects of CSC and nicotine. CSC exhibited a dose-dependent nicotine generalization, and interestingly, 1.0mg/kg of DHβE antagonized the discriminative effects of nicotine (0.4mg/kg) but not CSC (0.4mg/kg nicotine content). However, pretreatment with MLA had no effect. In the time-course study, CSC had a relatively longer half-life in terms of the discriminative-stimulus effects compared with nicotine alone. Taken together, the present findings indicate that CSC has a distinct influence on interoceptive effects relative to nicotine alone and that these differential effects might be mediated, at least in part, by the α4β2, but not the α7, nAChR. PMID:26996314

  16. Geometrical analysis of deformation band lozenges and their scaling relationships to fault lenses

    NASA Astrophysics Data System (ADS)

    Awdal, Abdullah; Healy, David; Alsop, G. Ian

    2014-09-01

    Deformation bands can influence fluid flow in sandstone hydrocarbon reservoirs and therefore, understanding the geometrical attributes of individual bands and their patterns is a critical step in quantifying their connectivity. We present a geometrical study of deformation band lozenges, which are rock volumes contained between deformation bands, and fault lenses, which are rock volumes bounded by slip surfaces in fault cores. We investigate the statistical trends among data sets for deformation band lozenges and fault lenses in sandstones from the Moray Firth (Scotland) and southeastern Utah (USA), and explore their potential correlation to other attributes of the fracture pattern and petrophysical properties. The aspect ratio of lozenges, that represents the ratio of length or height to the maximum thickness of a lozenge, displays an oblate-shaped geometry in relation to fault-zone orientation. The length-thickness scaling relationships of lozenges are statistically similar to lenses. The scaling relationships show a slope break between lozenges bounded by deformation bands and lenses bounded by slip surfaces in the fault core. This break is inferred to mark the boundary between the lozenge domain and lens domain, and is likely due to a deformation transition from distributed strain for deformation bands to localised strain for slip surfaces. Furthermore, the integration of geometrical analysis with an understanding of scaling properties can help to make better predictions of fractures and fault properties in subsurface reservoirs.

  17. Nicotine replacement products: poisoning in children.

    PubMed

    2014-05-01

    Nicotine is widely used in smoking cessation aids. They are marketed in many forms, including: chewing gum, sublingual tablets, lozenges, transdermal patches, cartridges for oral inhalation, and mouth spray. French poison control and toxico-vigilance centres identified 318 cases of exposure to nicotine replacement products in children under the age of 10 years between 2000 and 2010. The exposure provoked symptoms in 62 of these children, about two-thirds of whom were under the age of 4 years. A U.S. analysis identified 1768 cases of poisoning in children under the age of 6 years involving smokeless tobacco products, reported between 2006 and 2008.84% of these cases occurred in children under the age of 3 years. The first signs of nicotine poisoning are gastrointestinal (vomiting, diarrhoea), cardiovascular (tachycardia, hypertension) and neuropsychological (tremor of the extremities). With higher doses, these effects are rapidly followed by loss of consciousness, convulsions or respiratory failure. In children, poisoning can occur after ingestion of 1 mg of nicotine per kilogram of body weight. A dose of this magnitude is sometimes fatal in adults. Most cases of poisoning involving transdermal patches occur when a child finds an unused patch, or a used patch that an adult has discarded in a bin without taking proper precautions. Sometimes they involve patches that have become detached from an adult's skin. In practice, it is important to warn adults using smoking cessation aids containing nicotine that these products are dangerous PMID:24926513

  18. Nicotine and tobacco

    MedlinePlus

    Withdrawal from nicotine; Smoking - nicotine addiction and withdrawal; Smokeless tobacco - nicotine addiction; Cigar smoking; Pipe smoking; Smokeless snuff; Tobacco use; Chewing tobacco; Nicotine addiction and tobacco

  19. Zinc lozenges as cure for the common cold--a review and hypothesis.

    PubMed

    Eby, George A

    2010-03-01

    A 7-day reduction in duration of common colds was shown by Eby et al. in 1984 using 23mg zinc gluconate throat lozenges. Over the following 25years, 14 double-blind, placebo-controlled, randomized clinical trials produced widely differing results with about one-half showing success and the remainder showing failure. Positively charged, ionic zinc (iZn), but not bound zinc, is strongly astringent, antirhinoviral, increases interferon-gamma (IFN-gamma) 10-fold, inhibits intercellular adhesion molecule-1 (ICAM-1) and inhibits the release of vasoactive ingredients from mast cell granules. Solution equilibrium chemistry analytical techniques showed lozenge iZn fraction varying from 0% to 100% of total lozenge zinc between trials, with zinc acetate (ZA) releasing 100% iZn, zinc gluconate (ZG) releasing 72% iZn and other zinc compounds releasing much less or none at physiologic pH 7.4. Since only iZn has in vitro benefits, iZn variations are hypothesized to have produced the widely varying clinical results. In support of the iZn hypothesis, lozenge iZn and total daily iZn in trials were found highly correlated with reductions in common cold durations with statistical significance for mean duration (P<0.001) and median duration (P<0.004), while total zinc (iZn plus bound) showed no correlation with changes in duration. Duration reductions (mean 0 days, median 0.43 days) for multi-ligand ZG and ZA lozenges differed significantly from duration reductions (mean 3.37 days, median 2.9 days) for single ligand ZA and ZG lozenges (P<0.001) showing that additive ligands as flavor-masks damaged or eliminated efficacy. Five of 6 trials with lozenges whose zinc compositions had a first stability constant of 1.7 or less succeeded, while only 2 of 9 trials of lozenges with higher stability succeeded (P<0.02). From the strong, multiple statistical relationships found, it is inferred that iZn is the active ingredient in zinc lozenges for colds, as it is in vitro against rhinoviruses, and

  20. New Techniques for Augmenting Saliva Collection: Bacon Rules and Lozenge Drools

    PubMed Central

    Miočević, Olga; Warner, Melissa C.; Slowey, Paul D.; Shirtcliff, Elizabeth A.

    2015-01-01

    Purpose Saliva is a reliable, noninvasive, and cost-effective alternative to biomarkers measured in other biological fluids. Within certain populations, saliva sampling may be difficult because of insufficient saliva flow, which may compromise disease diagnosis or research integrity. Methods to improve flow rates (eg, administering citric acid, chewing gum, or collecting cotton) may compromise biomarker integrity, especially if the methods involve the presence of a collection aid in the oral cavity. Anecdotal strategies (eg, looking at pictures of food or imagining food) have not been evaluated to date. In this study, we evaluate whether 2 novel collection techniques improve saliva flow or interfere with assay of common biomarkers (ie, cortisol, dehydroepiandrosterone, and testosterone). We evaluate an over-the-counter anhydrous crystalline maltose lozenge intended to increase saliva production for patients with xerostomia long after the lozenge dissolves. We then evaluate whether the smell of freshly cooked bacon stimulates a pavlovian-type reflex. Methods Saliva was collected from 27 healthy young adults (aged 20-34 years; 12 men) on a basal day and a lozenge day, providing 5 samples at 15-minute intervals. Twenty participants then returned for the bacon day condition, providing 2 saliva samples with an interval of 15 minutes between samples. Collection times required to generate 2 mL of saliva across collection strategies were recorded, and then saliva samples were assayed for cortisol, dehydroepiandrosterone, and testosterone. Findings Repeated analysis of variance measures revealed that both the lozenges and bacon significantly decreased collection time compared with the passive drool collection on the basal day. No significant effects were found related to the quantification of cortisol, testosterone, or dehydroepiandrosterone when comparing lozenge or bacon to the basal day. In addition, bivariate correlations revealed that concentrations from time

  1. Nicotine Withdrawal

    PubMed Central

    McLaughlin, Ian; Dani, John A.; De Biasi, Mariella

    2015-01-01

    An aversive abstinence syndrome manifests 4–24 h following cessation of chronic use of nicotine-containing products. Symptoms peak on approximately the 3rd day and taper off over the course of the following 3–4 weeks. While the severity of withdrawal symptoms is largely determined by how nicotine is consumed, certain short nucleotide polymorphisms (SNPs) have been shown to predispose individuals to consume larger amounts of nicotine more frequently—as well as to more severe symptoms of withdrawal when trying to quit. Additionally, rodent behavioral models and transgenic mouse models have revealed that specific nicotinic acetylcholine receptor (nAChR) subunits, cellular components, and neuronal circuits are critical to the expression of withdrawal symptoms. Consequently, by continuing to map neuronal circuits and nAChR subpopulations that underlie the nicotine withdrawal syndrome—and by continuing to enumerate genes that predispose carriers to nicotine addiction and exacerbated withdrawal symptoms—it will be possible to pursue personalized therapeutics that more effectively treat nicotine addiction. PMID:25638335

  2. Nicotine Gum

    MedlinePlus

    ... gum is used to help people stop smoking cigarettes. Nicotine chewing gum should be used together with ... by your doctor.If you smoke your first cigarette more than 30 minutes after waking up, use ...

  3. Spin-lozenge thermodynamics and magnetic excitations in Na3RuO4

    SciTech Connect

    Haraldsen, Jason T; Stone, Matthew B; Lumsden, Mark D; Barnes, Ted {F E }; Jin, Rongying; Taylor, J. W.; Fernandez-Alonso, F

    2009-01-01

    We report inelastic and elastic neutron scattering, magnetic susceptibility, and heat capacity measurements of polycrystalline sodium ruthenate (Na3RuO4). Previous work suggests this material consists of isolated tetramers of S = 3/2 Ru5+ ions in a so-called lozenge configuration. Using a Heisenberg antiferromagnet Hamiltonian, we analytically determine the energy eigenstates for general spin S. From this model, the neutron scattering cross-sections for excitations associated with spin-3/2 tetramer configurations is determined. Comparison of magnetic susceptibility and inelastic neutron scattering results shows that the proposed lozenge model is not distinctly supported, but provides evidence that the system may be better described as a pair of non-interacting inequivalent dimers, i.e double dimers. However, the existence of long-range magnetic order below Tc ≈ 28 K immediately questions such a description. Although no evidence of the lozenge model is observed, future studies on single crystals may further clarify the appropriate magnetic Hamiltonian.

  4. Nicotine Transdermal Patch

    MedlinePlus

    ... patches are used to help people stop smoking cigarettes. They provide a source of nicotine that reduces ... cause harm to the fetus.do not smoke cigarettes or use other nicotine products while using nicotine ...

  5. Mutations in lozenge and D-Pax2 invoke ectopic patterned cell death in the developing Drosophila eye using distinct mechanisms.

    PubMed

    Siddall, Nicole A; Behan, Kristina Jackson; Crew, Jennifer R; Cheung, Tara L; Fair, Jason A; Batterham, Philip; Pollock, John Archie

    2003-04-01

    Mutations in the lozenge gene of Drosophila melanogaster elicit a pleiotropic set of adult phenotypes, including severe compound eye perturbations resulting from the defective recruitment of photoreceptors R1/6 and R7, cone and pigment cells. In this study, we show that excessive patterned apoptosis is evident at the same developmental stage in these lozenge mutants. In lozenge null mutants, apoptosis occurs prior to lozenge-dependent cell fate specification. A second gene, D-Pax2, genetically interacts with lozenge. Interestingly, D-Pax2 mutants also exhibit increased cell death, but slightly later in development than that in lozenge mutants. Although expression of the caspase inhibitor p35 eliminates death in both lozenge and D-Pax2 mutants, the lozenge mutant eye phenotypes persist because other normal Lozenge functions are still lacking. D-Pax2 eye phenotypes, in contrast, are dramatically altered in a p35 background, because cells that normally differentiate as cone and primary pigment cells are subsequently transformed into secondary pigment cells. This study leads us to propose that Lozenge, aside from its known role in gene regulation of cell-specific transcription factors, is required to contribute to the repression of cell death mechanisms, creating a permissive environment for the survival of undifferentiated cells in early eye development. Lack of lozenge expression increases the likelihood that an undifferentiated cell will initiate its default death program and die prematurely. The ectopic cell death evident in D-Pax2 mutants appears to arise from the cell fate transformation of cone cells into secondary pigment cells, either autonomously or as a result of defective signalling. PMID:12690448

  6. Time course of nicotine and cotinine incorporation into samples of nonsmokers' beard hair following a single dose of nicotine polacrilex.

    PubMed

    Bernert, John T; Alexander, Joseph R; Sosnoff, Connie S; McGuffey, James E

    2011-01-01

    Hair nicotine and cotinine have been proposed as longer-term markers of exposure to secondhand smoke. In this study, we evaluated the rate and extent of nicotine and cotinine deposition into beard hair among six male nonsmokers following a single exposure to 4 mg of nicotine in Nicorette(®) (nicotine polacrilex) gum. We collected beard hair samples daily for 12 days following exposure and urine samples for 6 days after exposure. Using liquid chromatographic-tandem mass spectrometric analysis, we found that both nicotine and cotinine could be detected in beard samples within 24 h of the exposure and reached a maximum of about 71 pg nicotine and 47 pg cotinine/mg hair, respectively, within 1-2 days, followed by a gradual decline. Compared to beard hair concentrations, nicotine, cotinine, and hydroxycotinine were excreted in urine at much higher levels and also peaked on the day after exposure (mean ± SD urine cotinine = 300 ± 183 ng/mL). Our results confirmed that both nicotine and cotinine can be measured in beard hair samples following a single dose of nicotine. However, both the time-course and extent of deposition of these analytes in beard hair in this study differed from the results reported previously from a similar evaluation. PMID:21219696

  7. Nicotine replacement therapy

    MedlinePlus

    ... If wearing the patch at night causes odd dreams, try sleeping without the patch. People who smoke ... cessation - nicotine replacement; Tobacco - nicotine replacement therapy References American Cancer Society. Guide to quitting smoking. Last revised ...

  8. The acute effects of daily nicotine intake on heart rate--a toxicokinetic and toxicodynamic modelling study.

    PubMed

    Gajewska, M; Worth, A; Urani, C; Briesen, H; Schramm, K-W

    2014-10-01

    Joint physiologically-based toxicokinetic and toxicodynamic (PBTK/TD) modelling was applied to simulate concentration-time profiles of nicotine, a well-known stimulant, in the human body following single and repeated dosing. Both kinetic and dynamic models were first calibrated by using in vivo literature data for the Caucasian population. The models were then used to estimate the blood and liver concentrations of nicotine in terms of the Area Under Curve (AUC) and the peak concentration (Cmax) for selected exposure scenarios based on inhalation (cigarette smoking), oral intake (nicotine lozenges) and dermal absorption (nicotine patches). The model simulations indicated that whereas frequent cigarette smoking gives rise to high AUC and Cmax in blood, the use of nicotine-rich dermal patches leads to high AUC and Cmax in the liver. Venous blood concentrations were used to estimate one of the most common acute effects, mean heart rate, both at rest and during exercise. These estimations showed that cigarette smoking causes a high peak heart rate, whereas dermal absorption causes a high mean heart rate over 48h. This study illustrates the potential of using PBTK/TD modelling in the safety assessment of nicotine-containing products. PMID:25066669

  9. Effects of nicotine gum on F waves in non-smokers.

    PubMed

    Strenge, H; Schmidt, G; Niederberger, U; Porschke, H; Schütz, H W

    1996-01-01

    The effects of chewing gum, containing 0 and 4 mg nicotine, on F waves were studied in healthy volunteers in a repeated measure design. F responses were recorded from the abductor pollicis brevis muscle following stimulation of the median nerve at the wrist. The persistence and various amplitude measures were analysed. Chewing a 4 mg nicotine gum, with a considerable rise in systemic nicotine (6.4-37.4 ng/ml), failed to produce significant effects on F wave parameters in relation to the placebo baseline. The analysis of different F wave amplitude ranges, however, revealed significant nicotine-induced changes: a dose-related decrease of F responses > or = 500 microV and an increase of F waves between 200-290 microV. This may be due to an activation of Renshaw cells in the spinal cord. PMID:8934149

  10. A novel Lozenge gene in silkworm, Bombyx mori regulates the melanization response of hemolymph.

    PubMed

    Xu, Man; Wang, Xue; Tan, Juan; Zhang, Kui; Guan, Xi; Patterson, Laurence H; Ding, Hanfei; Cui, Hongjuan

    2015-11-01

    Runt-related (RUNX) transcription factors are evolutionarily conserved either in vertebrate or invertebrate. Lozenge (Lz), a members of RUNX family as well as homologue of AML-1, functions as an important transcription factor regulating the hemocytes differentiation. In this paper, we identified and characterized RUNX family especially Lz in silkworm, which is a lepidopteran model insect. The gene expression analysis illustrated that BmLz was highly expressed in hemocytes throughout the whole development period, and reached a peak in glutonous stage. Over-expression of BmLz in silkworm accelerated the melanization process of hemolymph, and led to instantaneously up-regulation of prophenoloxidases (PPOs), which were key enzymes in the melanization process. Further down-regulation of BmLz expression by RNA interference resulted in the significant delay of melanization reaction of hemolymph. These findings suggested that BmLz regulated the melanization process of hemolymph by inducing PPOs expression, and played a critical role in innate immunity defense in silkworm. PMID:26164197

  11. Effects of Nicotine on Streptococcus gordonii Growth, Biofilm Formation, and Cell Aggregation.

    PubMed

    Huang, R; Li, M; Ye, M; Yang, K; Xu, X; Gregory, R L

    2014-12-01

    Streptococcus gordonii is a commensal species of human oral flora. It initiates dental biofilm formation and provides binding sites for later colonizers to attach to and generate mature biofilm. Smoking is the second highest risk factor for periodontal disease, and cigarette smoke extract has been reported to facilitate Porphyromonas gingivalis-S. gordonii dual-species biofilm formation. Our hypothesis is that nicotine, one of the most important and active components of tobacco, stimulates S. gordonii multiplication and aggregation. In the present study, S. gordonii planktonic cell growth (kinetic absorbance and CFU), biofilm formation (crystal violet stain and confocal laser scanning microscopy [CLSM]), aggregation with/without sucrose, and 11 genes that encode binding proteins or regulators of gene expression were investigated. Results demonstrated planktonic cell growth was stimulated by 1 to 4 mg/ml nicotine treatment. Biofilm formation was increased at 0.5 to 4 mg/ml nicotine. CLSM indicated bacterial cell mass was increased by 2 and 4 mg/ml nicotine, but biofilm extracellular polysaccharide was not significantly affected by nicotine. Cell aggregation was upregulated by 4, 8, and 16 mg/ml nicotine with sucrose and by 16 mg/ml nicotine without sucrose. Quantitative reverse transcriptase PCR indicated S. gordonii abpA, scaA, ccpA, and srtA were upregulated in planktonic cells by 2 mg/ml nicotine. In conclusion, nicotine stimulates S. gordonii planktonic cell growth, biofilm formation, aggregation, and gene expression of binding proteins. Those effects may promote later pathogen attachment to tooth surfaces, the accumulation of tooth calculus, and the development of periodontal disease in cigarette smokers. PMID:25217021

  12. Mechanisms of Nicotine Addiction

    SciTech Connect

    McGehee, Daniel

    2002-06-26

    Nicotine reinforces the use of tobacco products primarily through its interaction with specific receptor proteins within the brain's reward centers. A critical step in the process of addiction for many drugs, including nicotine, is the release of the neurotransmitter dopamine. A single nicotine exposure will enhance dopamine levels for hours, however, nicotinic receptors undergo both activation and then desensitization in minutes, which presents an important problem. How does the time course of receptor activity lead to the prolonged release of dopamine? We have found that persistent modulation of both inhibitory and excitatory synaptic connections by nicotine underlies the sustained increase in dopamine release. Because these inputs express different types of nicotinic receptors there is a coordinated shift in the balance of synaptic inputs toward excitation of the dopamine neurons. Excitatory inputs are turned on while inhibitory inputs are depressed, thereby boosting the brain's reward system.

  13. Mechanisms of Nicotine Addiction

    SciTech Connect

    McGehee, Daniel

    2009-06-26

    Nicotine reinforces the use of tobacco products primarily through its interaction with specific receptor proteins within the brain’s reward centers. A critical step in the process of addiction for many drugs, including nicotine, is the release of the neurotransmitter dopamine. A single nicotine exposure will enhance dopamine levels for hours, however, nicotinic receptors undergo both activation and then desensitization in minutes, which presents an important problem. How does the time course of receptor activity lead to the prolonged release of dopamine? We have found that persistent modulation of both inhibitory and excitatory synaptic connections by nicotine underlies the sustained increase in dopamine release. Because these inputs express different types of nicotinic receptors there is a coordinated shift in the balance of synaptic inputs toward excitation of the dopamine neurons. Excitatory inputs are turned on while inhibitory inputs are depressed, thereby boosting the brain’s reward system.

  14. Pharmacological Intervention of Nicotine Dependence

    PubMed Central

    Jain, Raka; Gupta, Tina

    2013-01-01

    Nicotine dependence is a major cause of mortality and morbidity all over the world. Various medications have been tried to treat nicotine dependence including nicotine replacement therapy, bupropion, and varenicline. A newer venture to nicotine dependence treatment is a nicotine vaccine which is yet to get footsteps in common practice. The present review assimilates various pharmacotherapeutic measures to address nicotine dependence. However, it is to be noted that psychological interventions, when combined with pharmacotherapy, offer the greatest benefits to the patients. PMID:24490153

  15. Harmful effects of nicotine

    PubMed Central

    Mishra, Aseem; Chaturvedi, Pankaj; Datta, Sourav; Sinukumar, Snita; Joshi, Poonam; Garg, Apurva

    2015-01-01

    With the advent of nicotine replacement therapy, the consumption of the nicotine is on the rise. Nicotine is considered to be a safer alternative of tobacco. The IARC monograph has not included nicotine as a carcinogen. However there are various studies which show otherwise. We undertook this review to specifically evaluate the effects of nicotine on the various organ systems. A computer aided search of the Medline and PubMed database was done using a combination of the keywords. All the animal and human studies investigating only the role of nicotine were included. Nicotine poses several health hazards. There is an increased risk of cardiovascular, respiratory, gastrointestinal disorders. There is decreased immune response and it also poses ill impacts on the reproductive health. It affects the cell proliferation, oxidative stress, apoptosis, DNA mutation by various mechanisms which leads to cancer. It also affects the tumor proliferation and metastasis and causes resistance to chemo and radio therapeutic agents. The use of nicotine needs regulation. The sale of nicotine should be under supervision of trained medical personnel. PMID:25810571

  16. Harmful effects of nicotine.

    PubMed

    Mishra, Aseem; Chaturvedi, Pankaj; Datta, Sourav; Sinukumar, Snita; Joshi, Poonam; Garg, Apurva

    2015-01-01

    With the advent of nicotine replacement therapy, the consumption of the nicotine is on the rise. Nicotine is considered to be a safer alternative of tobacco. The IARC monograph has not included nicotine as a carcinogen. However there are various studies which show otherwise. We undertook this review to specifically evaluate the effects of nicotine on the various organ systems. A computer aided search of the Medline and PubMed database was done using a combination of the keywords. All the animal and human studies investigating only the role of nicotine were included. Nicotine poses several health hazards. There is an increased risk of cardiovascular, respiratory, gastrointestinal disorders. There is decreased immune response and it also poses ill impacts on the reproductive health. It affects the cell proliferation, oxidative stress, apoptosis, DNA mutation by various mechanisms which leads to cancer. It also affects the tumor proliferation and metastasis and causes resistance to chemo and radio therapeutic agents. The use of nicotine needs regulation. The sale of nicotine should be under supervision of trained medical personnel. PMID:25810571

  17. Nicotine and sympathetic neurotransmission.

    PubMed

    Haass, M; Kübler, W

    1997-01-01

    Nicotine increases heart rate, myocardial contractility, and blood pressure. These nicotine-induced cardiovascular effects are mainly due to stimulation of sympathetic neurotransmission, as nicotine stimulates catecholamine release by an activation of nicotine acetylcholine receptors localized on peripheral postganglionic sympathetic nerve endings and the adrenal medulla. The nicotinic acetylcholine receptor is a ligand-gated cation channel with a pentameric structure and a central pore with a cation gate, which is essential for ion selectivity and permeability. Binding of nicotine to its extracellular binding site leads to a conformational change of the central pore, which results in the influx of sodium and calcium ions. The resulting depolarization of the sympathetic nerve ending stimulates calcium influx through voltage-dependent N-type calcium channels, which triggers the nicotine-evoked exocytotic catecholamine release. In the isolated perfused guinea-pig heart, cardiac energy depletion sensitizes cardiac sympathetic nerves to the norepinephrine-releasing effect of nicotine, as indicated by a leftward shift of the concentration-response curve, a potentiation of maximum transmitter release, and a delay of the tachyphylaxis of nicotine-evoked catecholamine release. This sensitization was also shown to occur in the human heart under in vitro conditions. Through the intracardiac release of norepinephrine, nicotine induces a beta-adrenoceptor-mediated increase in heart rate and contractility, and an alpha-adrenoceptor-mediated increase in coronary vasomotor tone. The resulting simultaneous increase in oxygen demand and coronary resistance has a detrimental effect on the oxygen balance of the heart, especially in patients with coronary artery disease. Sensitization of the ischemic heart to the norepinephrine-releasing effect of nicotine may be a trigger for acute cardiovascular events in humans, such as acute myocardial infarction and/or life

  18. Interaction between intra-oral cinnamaldehyde and nicotine assessed by psychophysical and physiological responses.

    PubMed

    Jensen, Tanja K; Andersen, Michelle V; Nielsen, Kent A; Arendt-Nielsen, Lars; Boudreau, Shellie A

    2016-08-01

    Cinnamaldehyde and nicotine activate the transient receptor potential subtype A1 (TRPA1) channel, which may cause burning sensations. This study investigated whether cinnamaldehyde modulates nicotine-induced psychophysical and physiological responses in oral tissues. Healthy non-smokers (n = 22) received, in a randomized, double-blind, crossover design, three different gums containing 4 mg of nicotine, 20 mg of cinnamaldehyde, or a combination thereof. Assessments of orofacial temperature and blood flow, blood pressure, heart rate, taste experience, and intra-oral pain/irritation area and intensity were performed before, during, and after a 10-min chewing regime. Cinnamaldehyde increased the temperature of the tongue and blood flow of the lip, and was associated with pain/irritation, especially in the mouth. Nicotine increased the temperature of the tongue and blood flow of the cheek, and produced pain/irritation in the mouth and throat. The combination of cinnamaldehyde and nicotine did not overtly change the psychophysical or physiological responses. Interestingly, half of the subjects responded to cinnamaldehyde as an irritant, and these cinnamaldehyde responders reported greater nicotine-induced pain/irritation areas in the throat. Whether sensitivity to cinnamaldehyde can predict the response to nicotine-induced oral irritation remains to be determined. A better understanding of the sensory properties of nicotine in the oral mucosa has important therapeutic implications because pain and irritation represent compliance issues for nicotine replacement products. PMID:27282133

  19. The incentive amplifying effects of nicotine are reduced by selective and non-selective dopamine antagonists in rats

    PubMed Central

    Palmatier, Matthew I.; Kellicut, Marissa R.; Sheppard, A. Brianna; Brown, Russell W.; Robinson, Donita L.

    2015-01-01

    Nicotine is a psychomotor stimulant with ‘reinforcement enhancing’ effects – the actions of nicotine in the brain increase responding for non-nicotine rewards. We hypothesized that this latter effect of nicotine depends on increased incentive properties of anticipatory cues; consistent with this hypothesis, multiple laboratories have reported that nicotine increases sign tracking, i.e. approach to a conditioned stimulus (CS), in Pavlovian conditioned-approach tasks. Incentive motivation and sign tracking are mediated by mesolimbic dopamine (DA) transmission and nicotine facilitates mesolimbic DA release. Therefore, we hypothesized that the incentive-promoting effects of nicotine would be impaired by DA antagonists. To test this hypothesis, separate groups of rats were injected with nicotine (0.4 mg/kg base) or saline prior to Pavlovian conditioning sessions in which a CS (30 s illumination of a light or presentation of a lever) was immediately followed by a sweet reward delivered in an adjacent location. Both saline and nicotine pretreated rats exhibited similar levels of conditioned approach to the reward location (goal tracking), but nicotine pretreatment significantly increased approach to the CS (sign tracking), regardless of type (lever or light). The DAD1 antagonist SCH-23390 and the DAD2/3 antagonist eticlopride reduced conditioned approach in all rats, but specifically reduced goal tracking in the saline pretreated rats and sign tracking in the nicotine pretreated rats. The non-selective DA antagonist flupenthixol reduced sign-tracking in nicotine rats at all doses tested; however, only the highest dose of flupenthixol reduced goal tracking in both nicotine and saline groups. The reductions in conditioned approach behavior, especially those by SCH-23390, were dissociated from simple motor suppressant effects of the antagonists. These experiments are the first to investigate the effects of dopaminergic drugs on the facilitation of sign

  20. Decreasing nicotinic receptor activity and the spatial learning impairment caused by the NMDA glutamate antagonist dizocilpine in rats

    PubMed Central

    Burke, Dennis A.; Heshmati, Pooneh; Kholdebarin, Ehsan; Levin, Edward D.

    2014-01-01

    Nicotinic systems have been shown by a variety of studies to be involved in cognitive function. Nicotinic receptors have an inherent property to become desensitized after activation. The relative role of nicotinic receptor activation vs. net receptor inactivation by desensitization in the cognitive effects of nicotinic drugs remains to be fully understood. In these studies, we tested the effects of the α7 nicotinic receptor antagonist methyllycaconitine (MLA), the α4β2 nicotinic receptor antagonist dihydro-β-erythroidine (DHβE), the nonspecific nicotinic channel blocker mecamylamine and the α4β2 nicotinic receptor desensitizing agent sazetidine-A on learning in a repeated acquisition test. Adult female Sprague-Dawley rats were trained on a repeated acquisition learning procedure in an 8-arm radial maze. MLA (1–4 mg/kg), DHβE (1–4 mg/kg), mecamylamine (0.125–0.5 mg/kg) or sazetidine-A (1 and 3 mg/kg) were administered in four different studies either alone or together with the NMDA glutamate antagonist dizocilpine (0.05 and 0.10 mg/kg). MLA significantly counteracted the learning impairment caused by dizocilpine. The overall choice accuracy impairment caused by dizocilpine was significantly attenuated by co-administration of DHβE. Low doses of the non-specific nicotinic antagonist mecamylamine also reduced dizocilpine-induced repeated acquisition impairment. Sazetidine-A reversed the accuracy impairment caused by dizocilpine. These studies provide evidence that a net decrease in nicotinic receptor activity can improve learning by attenuating learning impairment induced by NMDA glutamate blockade. This adds to evidence in cognitive tests that nicotinic antagonists can improve cognitive function. Further research characterizing the efficacy and mechanisms underlying nicotinic antagonist and desensitization induced cognitive improvement is warranted. PMID:25064338

  1. Pavlovian-Instrumental Transfer of the Discriminative Stimulus Effects of Nicotine and Ethanol in Rats

    ERIC Educational Resources Information Center

    Troisi, Joseph R., II

    2006-01-01

    To date, only 1 study has evaluated the impact of a Pavlovian drug conditional stimulus (CS) on operant responding. A within-subject operant 1-lever go/no-go (across sessions) design was used to evaluate the impact of Pavlovian contingencies on the discriminative stimulus effects of nicotine (0.4 mg/kg) and ethanol (800 mg/kg) in male Sprague…

  2. Zinc(II) in saliva: determination of concentrations produced by different formulations of zinc gluconate lozenges containing common excipients.

    PubMed

    Zarembo, J E; Godfrey, J C; Godfrey, N J

    1992-02-01

    A study of the pH of saliva produced by humans sucking hard candy lozenges containing zinc gluconate and citric acid demonstrated the probability that the formulation delivered an insignificant amount of the contained zinc as Zn2+. This could account for the negative results of several clinical studies of this lozenge and similar formulations as treatment for the common cold. Direct measurement of unbound Zn2+ in saliva from this and other zinc gluconate formulations was required to substantiate the inference from the pH study. A specific-ion-electrode assay method was developed. Using this method, it was found that saliva completely suppresses the ionization of zinc to free Zn2+ in the presence of citric acid or a 30-fold molar excess of mannitol plus sorbitol. Under the same conditions, however, the presence of an excess of glycine does not interfere with ionization to produce Zn2+. This finding supports the hypothesis that the positive clinical results of three studies were due to the use of formulations which release ionic zinc. PMID:1545350

  3. Genetic instability of the lozenge locus in Drosophila melanogaster: Characterization of the lz{sup 75V} allele

    SciTech Connect

    Voloshina, M.A.; Golubovskii, M.D.

    1995-12-01

    Genetic properties of lz{sup 75V}, an unstable allele of the lozenge locus, are described. The lz{sup 75V} allele appeared in progeny of a male from a Far East natural population of Drosophila melanogaster. Mutation of this allele produces a broad spectrum of mutant derivatives with phenotypes varying from normal to extreme. The arising alleles can be stable or unstable. Some lz{sup 75V} derivatives continuously preserve their spontaneous mutability in laboratory conditions, whereas other alleles of the same family show progressive stabilization at the intralocus or intrachromosome level. Instability of the lz{sup 75V}-bearing X chromosome is locus-specific: only the lozenge gene mutates with high frequency, while visible mutations at other loci rarely occur. As shown previously, the lz{sup 75V} allele appears to be caused by a P-element insertion. The appearance of spontaneous instability is discussed with regard to the general problem of transposition regulation in mobile elements. Different systems of hybrid dysgenesis, and, in particular, P elements are assumed to play an important role in induction of unstable mutations in nature. 24 refs., 5 tabs.

  4. Nicotine and health.

    PubMed

    2014-07-01

    Nicotine, an alkaloid derived from the leaves of tobacco plants (Nicotiana tabacum and Nicotiana rustica) is the primary addictive agent in tobacco products.(1,2) There are different ways of administering the various products including smoking cigarettes, chewing tobacco, holding moist snuff in the mouth, inhaling dry snuff through the nose, inhaling smoke from a waterpipe and inhaling vapour from an electronic cigarette.(3-6) It can be difficult differentiating the effects of nicotine from the many other toxic substances these products also contain. Here we review the pharmacological effects of nicotine but we will not review the well-known harmful effects of cigarettes, where it is primarily the toxins and carcinogens in tobacco smoke rather than the nicotine that cause illness and death.(7) A future article will consider the use of electronic cigarettes. PMID:25012148

  5. Republished: Nicotine and health.

    PubMed

    2014-01-01

    Nicotine, an alkaloid derived from the leaves of tobacco plants (Nicotiana tabacum and Nicotiana rustica) is the primary addictive agent in tobacco products.(1,2) There are different ways of administering the various products including smoking cigarettes, chewing tobacco, holding moist snuff in the mouth, inhaling dry snuff through the nose, inhaling smoke from a waterpipe and inhaling vapour from an electronic cigarette.(3-6) It can be difficult differentiating the effects of nicotine from the many other toxic substances these products also contain. Here we review the pharmacological effects of nicotine but we will not review the well-known harmful effects of cigarettes, where it is primarily the toxins and carcinogens in tobacco smoke rather than the nicotine that cause illness and death.(7) A future article will consider the use of electronic cigarettes. PMID:25428425

  6. Nicotine Oral Inhalation

    MedlinePlus

    ... class of medications called smoking cessation aids. It works by providing nicotine to your body to decrease ... want to try different schedules to see what works best for you.Ask your pharmacist or doctor ...

  7. Randomized Trial of Reduced-Nicotine Standards for Cigarettes

    PubMed Central

    Donny, Eric C.; Denlinger, Rachel L.; Tidey, Jennifer W.; Koopmeiners, Joseph S.; Benowitz, Neal L.; Vandrey, Ryan G.; al’Absi, Mustafa; Carmella, Steven G.; Cinciripini, Paul M.; Dermody, Sarah S.; Drobes, David J.; Hecht, Stephen S.; Jensen, Joni; Lane, Tonya; Le, Chap T.; McClernon, F. Joseph; Montoya, Ivan D.; Murphy, Sharon E.; Robinson, Jason D.; Stitzer, Maxine L.; Strasser, Andrew A.; Tindle, Hilary; Hatsukami, Dorothy K.

    2015-01-01

    BACKGROUND The Food and Drug Administration can set standards that reduce the nicotine content of cigarettes. METHODS We conducted a double-blind, parallel, randomized clinical trial between June 2013 and July 2014 at 10 sites. Eligibility criteria included an age of 18 years or older, smoking of five or more cigarettes per day, and no current interest in quitting smoking. Participants were randomly assigned to smoke for 6 weeks either their usual brand of cigarettes or one of six types of investigational cigarettes, provided free. The investigational cigarettes had nicotine content ranging from 15.8 mg per gram of tobacco (typical of commercial brands) to 0.4 mg per gram. The primary outcome was the number of cigarettes smoked per day during week 6. RESULTS A total of 840 participants underwent randomization, and 780 completed the 6-week study. During week 6, the average number of cigarettes smoked per day was lower for participants randomly assigned to cigarettes containing 2.4, 1.3, or 0.4 mg of nicotine per gram of tobacco (16.5, 16.3, and 14.9 cigarettes, respectively) than for participants randomly assigned to their usual brand or to cigarettes containing 15.8 mg per gram (22.2 and 21.3 cigarettes, respectively; P<0.001). Participants assigned to cigarettes with 5.2 mg per gram smoked an average of 20.8 cigarettes per day, which did not differ significantly from the average number among those who smoked control cigarettes. Cigarettes with lower nicotine content, as compared with control cigarettes, reduced exposure to and dependence on nicotine, as well as craving during abstinence from smoking, without significantly increasing the expired carbon monoxide level or total puff volume, suggesting minimal compensation. Adverse events were generally mild and similar among groups. CONCLUSIONS In this 6-week study, reduced-nicotine cigarettes versus standard-nicotine cigarettes reduced nicotine exposure and dependence and the number of cigarettes smoked. (Funded by

  8. Efficacy and Safety of Ambroxol Lozenges in the Treatment of Acute Uncomplicated Sore Throat - a Pooled Analysis.

    PubMed

    de Mey, C; Koelsch, S; Richter, E; Pohlmann, T; Sousa, R

    2016-07-01

    A pooled analysis is presented of 7 placebo-controlled RCT that investigated lozenges containing ambroxol for pain relief in acute sore throat.2 242 patients were treated with different ambroxol doses or control treatments, 2 183 were evaluable for efficacy. The present analysis is focused on the recommended dose of 20 mg (AXL20): 856 patients were treated with AXL20, 847 with matched placebo lozenges (PL).The average reduction in pain intensity over the first 3 h after the first AXL20 ranged from 38% to 52% of the maximum achievable effect (MAE). The overall treatment difference between AXL20 and PL was 11% (95% CI: 8-13%) of the MAE (post-hoc meta-analysis). The corresponding NNT was 6.0 (CI: 4.7-8.4) for an average pain reduction from baseline of 33% of the MAE over the first 3 h.71.9, 79.0, and 85.3% of the AXL20-patients scored the efficacy as "very good or good" at the end of the 1(st), 2(nd) and 3(rd) day, respectively, vs. 57.5, 64.4, and 70.4% of the PL-patients resulting in odds ratios of 1.9 (CI: 1.5-2.3) for the 1(st), 2.1 (CI: 1.7-2.6) for the 2(nd) and 2.43 (CI: 1.8-3.3) for the 3(rd) day.At the end of treatment 'no redness' or 'slightly red' was scored on pharyngeal inspection in 84.4% and 77.3% of AXL20- and PL-patients (OR: 1.6, CI: 1.3-1.9).AXL20-treatment was well tolerated and is safe and efficacious for acute uncomplicated sore throat of recent onset in adolescent and adult patients. PMID:27281448

  9. Evaluation of preoperative Strepsils lozenges on incidence of postextubation cough and sore throat in smokers undergoing anesthesia with endotracheal intubation

    PubMed Central

    Gupta, Divya; Agrawal, Sanjay; Sharma, Jagdish P.

    2014-01-01

    Post-operative sore throat (POST) is an undesirable side effect of endotracheal intubation. Pharmacological and non-pharmacological measures have been utilized for minimizing the morbidity caused by POST. We have tested use of Strepsils lozenges in providing efficacy for decreasing POST in smokers presenting for surgery under general anesthesia with endotracheal intubation. Materials and Methods: 100 patients, 20-65 years, American Society of Anesthesiologists (ASA) physical status I and II, either sex, history of smoking, posted for elective surgical procedure of more than 1 hour, requiring general anesthesia with endotracheal intubation were included and randomly divided into groups (n = 50) to receive Strepsils (Group A) and sugar candy (Group B). The patients were assessed for cough, sore throat, and hoarseness of voice after extubation, 30 min, 12 hrs, and 24 hrs after extubation. Results: At extubation no cough was seen in 39 (78%) patients (group A) compared to 23 (46%) patients (Group B), and mild cough in 22% (Group A) and 52% (Group B). Incidence of sore throat at extubation was lower in group A compared to Group B (P = 0.04). At other times of observations (30 min,12 hrs and 24 hrs) there was a significant decrease in incidence of sore throat in Group A compared to Group B (P = 0.000). Hoarseness of voice was not observed in any patient in either group. Conclusions: Use of preoperative Strepsils lozenges decreases incidence of POST and maybe utilized as a simple and cost-effective measure for decreasing the symptoms of POST and increasing the satisfaction of patients. PMID:24843341

  10. Effects of ethanol and nicotine on gastrin and somatostatin release in rats.

    PubMed

    Cho, C H; Ogle, C W; Wong, S H; Lam, S K

    1987-01-01

    An intravenous bolus injection of nicotine (1 mg/kg) markedly elevated gastric acid secretion; oral administration of ethanol (40%, 10 ml/kg) significantly increased arterial serum gastrin and somatostatin levels. Chronic pretreatment with oral nicotine (5 or 25 micrograms/ml in drinking tap water, for 10 days), but not acute pretreatment with a single oral dose of nicotine (2 or 4 mg/kg), inhibited the nicotine-induced gastric acid secretion and ethanol-induced gastrin and somatostatin release. Pretreatment subcutaneously with a ganglion-blocking dose of hexamethonium (10 mg/kg), however, inhibited nicotine-stimulated acid output and ethanol-evoked somatostatin secretion but not ethanol-induced gastrin release. It is concluded that ethanol-evoked gastrin secretion could be due to activation of specific sites which are not nicotinic receptors, but which are depressed by chronic nicotine pretreatment. On the other hand, the release of somatostatin by ethanol appears to be controlled by ganglionic receptors in the gut. PMID:2883103

  11. Nicotine trained as a negative feature passes the retardation-of-acquisition and summation tests of a conditioned inhibitor

    PubMed Central

    Murray, Jennifer E.; Walker, Andrew W.; Li, Chia; Wells, Nicole R.; Penrod, Rachel D.; Bevins, Rick A.

    2011-01-01

    Nicotine functions as a negative feature in a Pavlovian discriminated goal-tracking task. Whether withholding of responding to the conditional stimulus (CS) reflects nicotine functioning as a conditioned inhibitor is unknown. Accordingly, the present research sought to determine whether nicotine trained as a negative feature passed the retardation-of-acquisition and summation tests, thus characterizing it as a pharmacological (interoceptive) conditioned inhibitor. In the retardation test, rats received either nicotine (0.4 mg/kg) or chlordiazepoxide (5 mg/kg) negative feature training in which the drug state signaled when a 15-sec light CS would not be paired with sucrose; light was paired with sucrose on intermixed saline sessions. Following acquisition of the discrimination, both groups received nicotine CS training in which sucrose was intermittently available on nicotine but not intermixed saline sessions. Acquisition of conditioned responding to the nicotine CS was slower in the nicotine negative feature group than in the chlordiazepoxide negative feature group. In the summation test, rats were assigned to either the nicotine negative feature group or a pseudoconditioning control. In this control, the light CS was paired with sucrose on half the nicotine and half the saline sessions. Both groups also received excitatory training in which a white noise CS was paired with sucrose. The summation test consisted of presenting the white noise in conjunction with nicotine. Conditioned responding evoked by the white noise was decreased in the negative feature but not the pseudoconditioning group. Combined, the results provide the first evidence that an interoceptive stimulus (nicotine) can become a conditioned inhibitor. PMID:21693633

  12. Pavlovian Extinction of the Discriminative Stimulus Effects of Nicotine and Ethanol in Rats Varies as a Function of Context

    ERIC Educational Resources Information Center

    Troisi, Joseph R., II

    2011-01-01

    Operant extinction contingencies can undermine the discriminative stimulus effects of drugs. Here, nicotine (0.4 mg/kg) and ethanol (0.8 g/kg) first functioned as either an S[superscript D] or S[superscript Delta], in a counterbalanced one-lever go/no-go (across sessions) operant drug discrimination procedure. Pavlovian extinction in the training…

  13. BEHAVIORAL MECHANISMS UNDERLYING NICOTINE REINFORCEMENT

    PubMed Central

    Rupprecht, Laura E.; Smith, Tracy T.; Schassburger, Rachel L.; Buffalari, Deanne M.; Sved, Alan F.; Donny, Eric C.

    2015-01-01

    Cigarette smoking is the leading cause of preventable deaths worldwide and nicotine, the primary psychoactive constituent in tobacco, drives sustained use. The behavioral actions of nicotine are complex and extend well beyond the actions of the drug as a primary reinforcer. Stimuli that are consistently paired with nicotine can, through associative learning, take on reinforcing properties as conditioned stimuli. These conditioned stimuli can then impact the rate and probability of behavior and even function as conditioning reinforcers that maintain behavior in the absence of nicotine. Nicotine can also act as a conditioned stimulus, predicting the delivery of other reinforcers, which may allow nicotine to acquire value as a conditioned reinforcer. These associative effects, establishing non-nicotine stimuli as conditioned stimuli with discriminative stimulus and conditioned reinforcing properties as well as establishing nicotine as a conditioned stimulus, are predicted by basic conditioning principles. However, nicotine can also act non-associatively. Nicotine directly enhances the reinforcing efficacy of other reinforcing stimuli in the environment, an effect that does not require a temporal or predictive relationship between nicotine and either the stimulus or the behavior. Hence, the reinforcing actions of nicotine stem both from the primary reinforcing actions of the drug (and the subsequent associative learning effects) as well as the reinforcement enhancement action of nicotine which is non-associative in nature. Gaining a better understanding of how nicotine impacts behavior will allow for maximally effective tobacco control efforts aimed at reducing the harm associated with tobacco use by reducing and/or treating its addictiveness. PMID:25638333

  14. Waterpipe tobacco products: nicotine labelling versus nicotine delivery

    PubMed Central

    Vansickel, Andrea R; Shihadeh, Alan; Eissenberg, Thomas

    2013-01-01

    Background Waterpipe tobacco package labelling typically indicates “0.0% tar” and “0.05% or 0.5% nicotine”. Objective To determine the extent to which nicotine labeling is related to nicotine delivery. Methods 110 waterpipe smokers engaged in a 45-minute waterpipe smoking session. Puff topography and plasma nicotine were measured. Three waterpipe tobacco brands were used: Nakhla (0.5% nicotine), Starbuzz (0.05% nicotine), and Al Fakher (0.05% nicotine). Data were analyzed by one-way ANOVA. Results Topography did not differ across brands. Peak plasma nicotine varied significantly across brands. Al Fakher had the highest nicotine delivery (11.4 ng/ml) followed by Nakhla (9.8 ng/ml) and Starbuzz (5.8 ng/ml). Conclusions Nicotine labelling on waterpipe tobacco products does not reflect delivery; smoking a brand with a “0.05% nicotine” label led to greater plasma nicotine levels than smoking a brand with a “0.5% nicotine” label. Waterpipe tobacco products should be labelled in a manner that does not mislead consumers. PMID:21636612

  15. Nicotinic Receptors in Neurodegeneration

    PubMed Central

    Posadas, Inmaculada; López-Hernández, Beatriz; Ceña, Valentín

    2013-01-01

    Many studies have focused on expanding our knowledge of the structure and diversity of peripheral and central nicotinic receptors. Nicotinic acetylcholine receptors (nAChRs) are members of the Cys-loop superfamily of pentameric ligand-gated ion channels, which include GABA (A and C), serotonin, and glycine receptors. Currently, 9 alpha (α2-α10) and 3 beta (β2-β4) subunits have been identified in the central nervous system (CNS), and these subunits assemble to form a variety of functional nAChRs. The pentameric combination of several alpha and beta subunits leads to a great number of nicotinic receptors that vary in their properties, including their sensitivity to nicotine, permeability to calcium and propensity to desensitize. In the CNS, nAChRs play crucial roles in modulating presynaptic, postsynaptic, and extrasynaptic signaling, and have been found to be involved in a complex range of CNS disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, Tourette´s syndrome, anxiety, depression and epilepsy. Therefore, there is growing interest in the development of drugs that modulate nAChR functions with optimal benefits and minimal adverse effects. The present review describes the main characteristics of nAChRs in the CNS and focuses on the various compounds that have been tested and are currently in phase I and phase II trials for the treatment of neurodegenerative diseases including PD, AD and age-associated memory and mild cognitive impairment. PMID:24179465

  16. Vaccines against nicotine.

    PubMed

    Cerny, Erich H; Cerny, Thomas

    2009-04-01

    Medications against any dependence-inducing drug face a dilemma: if they are efficient, they will induce withdrawal symptoms and the patient is likely to stop taking his medication. Anti drug vaccines are irreversible, provide protection over years and need booster injections far beyond the critical phase of acute withdrawal symptoms. Interacting rather with the drug in the blood than with a receptor in the brain, the vaccines are, in addition, free of side effects due to central interaction. For drugs like nicotine interacting with different types of receptors in many organs, this is a further advantage. There are three reasons that anti drug vaccines have first been developed against nicotine. Firstly, in most parts of the world 20 to 50% of the adult population smoke and any smoking cessation treatment will have an important impact on public health and be commercially a very attractive product. The second reason are the smokers themselves, who would like to quit in significant numbers and who have shown good compliance for any form of treatment. Thirdly, the quantities of cocaine or heroine taken by dependant persons are higher than the quantity of nicotine per cigarette, which makes an anti nicotine vaccine the easier vaccine project. Three anti nicotine vaccines are today in an advanced stage of clinical evaluation. We report here how those vaccines work, on the progress of the trials and future developments to expect. Results show that the efficiency of the vaccines is directly related to the antibody levels of the probates, a fact which will help to optimize further the vaccine effect. We expect the vaccines to appear on the market during a time window between 2009 and 2011. PMID:19276649

  17. Hydrogenation behavior of the R4MgCo (R=Y, La, Nd, Tb) compounds

    NASA Astrophysics Data System (ADS)

    Shtender, V. V.; Paul-Boncour, V.; Riabov, A. B.; Denys, R. V.; Zavaliy, I. Yu.

    2015-09-01

    The hydrogen absorption properties of the R4MgCo compounds (R=Y, La, Nd, Tb; str. type Gd4RhIn; sp.gr. F 4 bar 3 m) have been studied for the first time. It was shown that their hydrogen storage capacity reaches about 2 wt%. At low pressure hydrogenation and moderately elevated temperatures the formed hydrides preserve the original structure of the metallic matrix. The crystal structure of the R4MgCoHx hydrides have been determined by XRD. Experimental hydrogen storage capacity (12 at.H/f.u. for Y4MgCo) is in good agreement with the theoretically calculated models, which allow also to estimate the distribution of H-atoms in metal lattice. TDS and DSC experiments demonstrated the multistep desorption process. XRD studies of the Tb4MgCoHx sample after TDS demonstrated the formation of TbH2 as the main phase and disproportionation of the parent compound.

  18. Multi-Sensor Approach for the Monitoring of Halitosis Treatment via Lactobacillus brevis (CD2)-Containing Lozenges--A Randomized, Double-Blind Placebo-Controlled Clinical Trial.

    PubMed

    Marchetti, Enrico; Tecco, Simona; Santonico, Marco; Vernile, Chiara; Ciciarelli, Daniele; Tarantino, Ester; Marzo, Giuseppe; Pennazza, Giorgio

    2015-01-01

    The aim of this randomized clinical trial was to evaluate whether a recently described multi-sensor approach called BIONOTE(®) is accurate enough to verify the efficacy of treatment of patients with halitosis. A treatment with Lactobacillus brevis (CD2)-containing lozenges, compared with placebo was tested. The BIONOTE(®) was compared with traditional techniques used to detect halitosis: OralChroma™ and two calibrated odor judges enrolled for the organoleptic assessments. Twenty patients (10 treated and 10 placebo), suffering from active phase halitosis were included in the study. Treatment consisted of Lactobacillus brevis (CD2)-containing lozenges or placebo, 4 tablets/day for 14 days. t0 was before the beginning of the study; t1 was day 7 and t2 was day 14. The effectiveness of treatment was assessed through: (1) Rosenberg score; (2) Winkel tongue coating index (WTCI) anterior and posterior; (2) OralChroma™; (3) the new developed multi-sensor approach, called BIONOTE(®) (test technique). Only the WTCI anterior revealed statistically significant changes between t0 and t2 data (p = 0.014) in the treated group. Except for the WTCI anterior, all diagnostic methods revealed the lack of effectiveness for halitosis of a 14-days treatment with Lactobacillus brevis (CD2)-containing lozenges. The BIONOTE(®) multisensor system seems accurate in addition to OralChroma™ to assess the initial condition of halitosis and its mitigation during treatment. PMID:26266414

  19. Modeling nicotine addiction in rats.

    PubMed

    Caille, Stephanie; Clemens, Kelly; Stinus, Luis; Cador, Martine

    2012-01-01

    Among the human population, 15% of drug users develop a pathological drug addiction. This figure increases substantially with nicotine, whereby more than 30% of those who try smoking develop a nicotine addiction. Drug addiction is characterized by compulsive drug-seeking and drug-taking behaviors (craving), and loss of control over intake despite impairment in health, social, and occupational functions. This behavior can be accurately modeled in the rat using an intravenous self-administration (IVSA) paradigm. Initial attempts at establishing nicotine self-administration had been problematic, yet in recent times increasingly reliable models of nicotine self-administration have been developed. The present article reviews different characteristics of the nicotine IVSA model that has been developed to examine nicotine reinforcing and motivational properties in rats. PMID:22231818

  20. Intravenous and oral suicidal e-liquid poisonings with confirmed nicotine and cotinine concentrations.

    PubMed

    Sommerfeld, Karina; Łukasik-Głębocka, Magdalena; Kulza, Maksymilian; Drużdż, Artur; Panieński, Paweł; Florek, Ewa; Zielińska-Psuja, Barbara

    2016-05-01

    The increasing availability of e-cigarettes is a potential toxicological concern. E-cigarettes appeared on the Polish market in 2006, and since 2009 they have been widely available with a new source of nicotine, the so-called e-liquid. In this paper two cases of suicidal oral and intravenous poisonings with the e-liquid are described. The clinical courses of these poisonings are presented. Nicotine and cotinine concentrations in the patient's blood were determined using high performance liquid chromatography with diode array detection. In the course of intoxication patient No. 1, classic symptoms of acute nicotine poisoning without convulsions were observed. Nicotine and cotinine concentrations measured in serum were 0.096 and 4.4mg/L, respectively. The case of patient No. 2, admission with no typical symptoms of nicotine poisoning was identified, except unconsciousness and slow respiration. Nicotine and cotinine concentrations in the serum at the time of No. 2 admissions were determined to be 0.8 and 1.3mg/L, respectively. With the increasing number of e-liquid poisonings cases, it should be aware that these products can be a readily available source of poison. PMID:27020616

  1. Neural effects of nicotine during auditory selective attention in smokers: an event-related potential study.

    PubMed

    Knott, Verner; Blais, Crystal; Scherling, Carole; Camarda, Jordan; Millar, Anne; Fisher, Derek; McIntosh, Judy

    2006-01-01

    Acute nicotine has been found to improve task performance in smokers after smoking abstinence, but the attentional processes mediating these improvements are unclear. Since scalp-recorded event-related potentials (ERPs) have been shown to be sensitive indicators of selective attention, the effects of acutely administered nicotine were examined on ERPs and concomitant behavioural performance measures in an auditory selective attention task. Ten (6 males) overnight smoking-abstinent cigarette smokers received nicotine gum (4 mg) in a randomized, double-blind, placebo-controlled, crossover design. In a dichotic listening task [which required participants to attend and detect (target) deviant stimuli in one ear and to ignore similar stimuli in the other ear] which included ERP recordings and assessment of response speed and accuracy measures, nicotine gum failed to alter behavioural performance or amplitudes of ERP components sensitive to selective attention [reflected in the N100 and negative difference (Nd) component] or to pre-attentive detection of acoustic change [reflected in the mismatch negativity (MMN) component]. However, nicotine did influence the speed of these voluntary selective processes, as reflected by shortened latencies of the early Nd component. The findings are discussed in relation to the stimulus filter theory of smoking, and with respect to nicotine's actions on involuntary and controlled aspects of selective attention processes. PMID:16601362

  2. Effects of acute nicotine on prepulse inhibition of auditory change-related cortical responses.

    PubMed

    Kodaira, Minori; Tsuruhara, Aki; Motomura, Eishi; Tanii, Hisashi; Inui, Koji; Kakigi, Ryusuke

    2013-11-01

    Prepulse inhibition (PPI) of startle is a measure of inhibitory function in which a weak leading stimulus suppresses the startle response to an intense stimulus. Usually, startle blink reflexes to an intense sound are used for measuring PPI. A recent magnetoencephalographic study showed that a similar phenomenon is observed for auditory change-related cortical response (Change-N1m) to an abrupt change in sound features. It has been well established that nicotine enhances PPI of startle. Therefore, in the present magnetoencephalographic study, the effects of acute nicotine on PPI of the Change-N1m were studied in 12 healthy subjects (two females and 10 males) under a repeated measures and placebo-controlled design. Nicotine (4 mg) was given as nicotine gum. The test Change-N1m response was elicited with an abrupt increase in sound pressure by 6 dB in a continuous background sound of 65 dB. PPI was produced by an insertion of a prepulse with a 3-dB-louder or 6-dB-weaker sound pressure than the background 75 ms before the test stimulus. Results show that nicotine tended to enhance the test Change-N1m response and significantly enhanced PPI for both prepulses. Therefore, nicotine's enhancing effect on PPI of the Change-N1m was similar to that on PPI of the startle. The present results suggest that the two measures share at least some mechanisms. PMID:23933145

  3. Nicotine and periodontal tissues

    PubMed Central

    Malhotra, Ranjan; Kapoor, Anoop; Grover, Vishakha; Kaushal, Sumit

    2010-01-01

    Tobacco use has been recognized to be a significant risk factor for the development and progression of periodontal disease. Its use is associated with increased pocket depths, loss of periodontal attachment, alveolar bone and a higher rate of tooth loss. Nicotine, a major component and most pharmacologically active agent in tobacco is likely to be a significant contributing factor for the exacerbation of periodontal diseases. Available literature suggests that nicotine affects gingival blood flow, cytokine production, neutrophil and other immune cell function; connective tissue turnover, which can be the possible mechanisms responsible for overall effects of tobacco on periodontal tissues. Inclusion of tobacco cessation as a part of periodontal therapy encourages dental professionals to become more active in tobacco cessation counseling. This will have far reaching positive effects on our patients’ oral and general health. PMID:20922084

  4. Nicotine intake by snuff users.

    PubMed Central

    Russell, M A; Jarvis, M J; Devitt, G; Feyerabend, C

    1981-01-01

    Blood nicotine and cotinine concentrations were measured in 27 volunteers before and after taking snuff. Within 10 minutes after snuffing blood nicotine concentrations were comparable to those obtained after the 10 minutes or so that it takes to smoke a cigarette. Nicotine intake from snuffing was related to the experience of the snuffer. In daily and occasional snuffers increases in plasma nicotine concentrations averaged 77.7 and 12.3 nmol/l (12.6 and 2.0 ng/ml) respectively, while the novices showed no appreciable increase. The increase shown by thea daily snuffers was comparable to the average increase of 62.3 nmol/l (10.1 ng/ml) obtained from a single cigarette by a group of heavy smokers. The peak nicotine concentrations in the daily snuffers were also similar to the peak values in 136 heavy smokers--222.6 and 226-3 nmol/l (36.1 and 36.7 ng/ml), respectively. Unusual multiple-dose snuffing produced massive increases in plasma nicotine to concentrations that have never been recorded in smokers. The similarity of the concentrations produced by regular daily snuffing and regular daily smoking suggests that the plasma nicotine concentration has some controlling influence over the self-regulation of these two quite different forms of tobacco use. The rapid absorption of nicotine from snuff confirms its potential as an acceptable and relatively harmless substitute for smoking. PMID:6794710

  5. Preparation and clinical evaluation of a novel lozenge containing polaprezinc, a zinc-L-carnosine, for prevention of oral mucositis in patients with hematological cancer who received high-dose chemotherapy.

    PubMed

    Hayashi, Hiroko; Kobayashi, Ryo; Suzuki, Akio; Yamada, Yuto; Ishida, Masayuki; Shakui, Toshinobu; Kitagawa, Junichi; Hayashi, Hideki; Sugiyama, Tadashi; Takeuchi, Hirofumi; Tsurumi, Hisashi; Itoh, Yoshinori

    2016-08-01

    We previously reported that oral ingestion of polaprezinc, a zinc-L-carnosine, suspended in sodium alginate solution prevents oral mucositis in patients receiving radiotherapy or high-dose chemotherapy. In the present study, we developed a novel preparation of polaprezinc and evaluated clinical effect of the lozenge preparation in patients receiving high-dose chemotherapy for hematopoietic stem cell transplantation. The preparation contained 18.75 mg polaprezinc in a tablet and showed an excellent uniformity and stability up to 24 weeks after storage under room temperature. The incidence rate of grade ≥ 2 oral mucositis was 74 % in patients without premedication, whereas the rate was remarkably reduced in patients receiving the suspension (23 %) or lozenge (13 %) of polaprezinc (P < 0.01). The use of non-opioid analgesic drugs such as anti-inflammatory agents and local anesthetics for oral pain was also greatly reduced by polaprezinc suspension or its lozenge (16 % for suspension and 13 % for lozenge compared with 89 % with no premedication, P < 0.01). These findings suggest that polaprezinc lozenge is simple to apply and highly effective for prevention of oral mucositis associated with high-dose chemotherapy for hematopoietic stem cell transplantation. PMID:27418192

  6. Nicotinic Regulation of Energy Homeostasis

    PubMed Central

    2012-01-01

    Introduction: The ability of nicotine, the primary psychoactive substance in tobacco smoke, to regulate appetite and body weight is one of the factors cited by smokers that prevents them from quitting and is the primary reason for smoking initiation in teenage girls. The regulation of feeding and metabolism by nicotine is complex, and recent studies have begun to identify nicotinic acetylcholine receptor (nAChR) subtypes and circuits or cell types involved in this regulation. Discussion: We will briefly describe the primary anatomical and functional features of the input, output, and central integration structures of the neuroendocrine systems that regulate energy homeostasis. Then, we will describe the nAChR subtypes expressed in these structures in mammals to identify the possible molecular targets for nicotine. Finally, we will review the effects of nicotine and its withdrawal on feeding and energy metabolism and attribute them to potential central and peripheral cellular targets. PMID:22990212

  7. [Nicotinic acid and nicotinamide].

    PubMed

    Kobayashi, M; Shimizu, S

    1999-10-01

    Nicotinic acid and nicotinamide are called niacin. They are the antipellagra vitamin essential to many animals for growth and health. In human being, niacin is believed necessary together with other vitamins for the prevention and cure of pellagra. Niacin is widely distributed in nature; appreciable amounts are found in liver, fish, yeast and cereal grains. Nicotinamide is a precursor of the coenzyme NAD and NADP. Some of the most understood metabolic processes that involve niacin are glycolysis, fatty acid synthesis and respiration. Niacin is also related to the following diseases: Hartnup disease; blue diaper syndrome; tryptophanuria; hydroxykynureninuria; xanthurenic aciduria; Huntington's disease. PMID:10540864

  8. Nicotine and the adolescent brain

    PubMed Central

    Yuan, Menglu; Cross, Sarah J; Loughlin, Sandra E; Leslie, Frances M

    2015-01-01

    Adolescence encompasses a sensitive developmental period of enhanced clinical vulnerability to nicotine, tobacco, and e-cigarettes. While there are sociocultural influences, data at preclinical and clinical levels indicate that this adolescent sensitivity has strong neurobiological underpinnings. Although definitions of adolescence vary, the hallmark of this period is a profound reorganization of brain regions necessary for mature cognitive and executive function, working memory, reward processing, emotional regulation, and motivated behavior. Regulating critical facets of brain maturation are nicotinic acetylcholine receptors (nAChRs). However, perturbations of cholinergic systems during this time with nicotine, via tobacco or e-cigarettes, have unique consequences on adolescent development. In this review, we highlight recent clinical and preclinical data examining the adolescent brain's distinct neurobiology and unique sensitivity to nicotine. First, we discuss what defines adolescence before reviewing normative structural and neurochemical alterations that persist until early adulthood, with an emphasis on dopaminergic systems. We review how acute exposure to nicotine impacts brain development and how drug responses differ from those seen in adults. Finally, we discuss the persistent alterations in neuronal signaling and cognitive function that result from chronic nicotine exposure, while highlighting a low dose, semi-chronic exposure paradigm that may better model adolescent tobacco use. We argue that nicotine exposure, increasingly occurring as a result of e-cigarette use, may induce epigenetic changes that sensitize the brain to other drugs and prime it for future substance abuse. PMID:26018031

  9. Mecamylamine reduces some EEG effects of nicotine chewing gum in humans.

    PubMed

    Pickworth, W B; Herning, R I; Henningfield, J E

    1988-05-01

    Spontaneous EEG was recorded in nine cigarette smokers who had been abstinent from tobacco for 12 hr. Subjects were treated with a capsule containing either centrally acting nicotine blocker, mecamylamine (10 mg), or placebo. At each of three 60-min intervals after the capsule was ingested, the subjects chewed two pieces of gum containing a total of 0, 4 or 8 mg of nicotine. Nicotine and mecamylamine dose combinations were randomized across subjects. Two three-minute periods of spontaneous EEG were recorded before the capsule and before and after gum chewing from bipolar electrode montages at the following positions: Cz-T5, Cz-T6, Cz-F7 and Cz-F8. During one period the subjects relaxed with eyes closed, in the other period they performed a math task with eyes open. When the drugs were given individually, mecamylamine decreased beta power and nicotine gum (4 and 8 mg) increased alpha frequency. Mecamylamine pretreatment prevented the increase in alpha frequency caused by the 4 mg gum dose but not the 8 mg dose. Alpha power was increased by the 8 mg gum dose and that increase was prevented by mecamylamine. Self-reported ratings of the "strength" of the gum were significantly diminished by mecamylamine pretreatment. The data are consistent with the results of earlier studies which indicate that the effects of tobacco administration and withdrawal are mediated by central actions of nicotine. PMID:3174738

  10. Pharmacodynamics of nicotine: implications for rational treatment of nicotine addiction.

    PubMed

    Benowitz, N L

    1991-05-01

    Rational treatment of the pharmacologic aspects of tobacco addiction includes nicotine substitution therapy. Understanding the pharmacodynamics of nicotine and its role in the addiction process provides a basis for rational therapeutic intervention. Pharmacodynamic considerations are discussed in relation to the elements of smoking cessation therapy: setting objectives, selecting appropriate medication and dosing form, selecting the optimal doses and dosage regimens, assessing therapeutic outcome, and adjusting therapy to optimize benefits and minimize risks. PMID:1859911

  11. Presenting your structures: the CCP4mg molecular-graphics software

    PubMed Central

    McNicholas, S.; Potterton, E.; Wilson, K. S.; Noble, M. E. M.

    2011-01-01

    CCP4mg is a molecular-graphics program that is designed to give rapid access to both straightforward and complex static and dynamic representations of macromolecular structures. It has recently been updated with a new interface that provides more sophisticated atom-selection options and a wizard to facilitate the generation of complex scenes. These scenes may contain a mixture of coordinate-derived and abstract graphical objects, including text objects, arbitrary vectors, geometric objects and imported images, which can enhance a picture and eliminate the need for subsequent editing. Scene descriptions can be saved to file and transferred to other molecules. Here, the substantially enhanced version 2 of the program, with a new underlying GUI toolkit, is described. A built-in rendering module produces publication-quality images. PMID:21460457

  12. Nicotinic Receptor Antagonists as Treatments for Nicotine Abuse

    PubMed Central

    Crooks, Peter A.; Bardo, Michael T.; Dwoskin, Linda P.

    2014-01-01

    Despite the proven efficacy of current pharmacotherapies for tobacco dependence, relapse rates continue to be high, indicating that novel medications are needed. Currently, several smoking cessation agents are available, including varenicline (Chantix®), bupropion (Zyban®), and cytisine (Tabex®). Varenicline and cytisine are partial agonists at the α4β2* nicotinic acetylcholine receptor (nAChR). Bupropion is an antidepressant but is also an antagonist at α3β2* ganglionic nAChRs. The rewarding effects of nicotine are mediated, in part, by nicotine-evoked dopamine (DA) release leading to sensitization, which is associated with repeated nicotine administration and nicotine addiction. Receptor antagonists that selectivity target central nAChR subtypes mediating nicotine-evoked DA release should have efficacy as tobacco use cessation agents with the therapeutic advantage of a limited side-effect profile. While α-conotoxin MII (α-CtxMII)-insensitive nAChRs (e.g., α4β2*) contribute to nicotine-evoked DA release, these nAChRs are widely distributed in the brain, and inhibition of these receptors may lead to nonselective and untoward effects. In contrast, α-CtxMII-sensitive nAChRs mediating nicotine-evoked DA release offer an advantage as targets for smoking cessation, due to their more restricted localization primarily to dopaminergic neurons. Small drug-like molecules that are selective antagonists at α-CtxMII-sensitive nAChR subtypes that contain α6 and β2 subunits have now been identified. Early research identified a variety of quaternary ammonium analogs that were potent and selective antagonists at nAChRs mediating nicotine-evoked DA release. More recent data have shown that novel, non-quaternary bis-1,2,5,6-tetrahydropyridine analogs potently inhibit (IC50<1 nM) nicotine-evoked DA release in vitro by acting as antagonists at α-CtxMII-sensitive nAChR subtypes; these compounds also decrease NIC self-administration in rats. PMID:24484986

  13. Nicotine Reduction: Strategic Research Plan

    PubMed Central

    2013-01-01

    Background: Reducing nicotine content in cigarettes and other combustible products to levels that are not reinforcing or addictive has the potential to substantially reduce tobacco-related morbidity and mortality. The authority to reduce nicotine levels as a regulatory measure is provided in the U.S. Family Smoking Prevention and Tobacco Control Act and is consistent with the general regulatory powers envisioned under the relevant articles of the World Health Organization’s Framework Convention on Tobacco Control. Many experts have considered reducing nicotine in cigarettes to be a feasible national policy approach, but more research is necessary. Purpose: This article describes proceedings from a conference that had the goals of identifying specific research gaps, describing methods and measures to consider for addressing these gaps, and considering ways to foster collaboration. Results and Conclusion: Identified research gaps included determining the dose of nicotine that would be optimal for reducing and extinguishing cigarette use, examining approaches for reducing nicotine levels in the general and special populations of smokers, understanding how constituents other than nicotine may contribute to the reinforcing effects of tobacco, and identifying unintended consequences to determine ways to mitigate them. Methods that can be used ranged from brain imaging to large human clinical trials. The development and availability of valid biomarkers of exposure and effect are important. Infrastructures to facilitate collaboration need to be established. PMID:23100460

  14. The influence of acute or chronic nicotine treatment on ethanol-induced gastric mucosal damage in rats.

    PubMed

    Cho, C H; Chen, B W; Hui, W M; Lam, S K

    1990-01-01

    The influences of acute or chronic nicotine pretreatment on ethanol-induced changes on gastric secretion, mucosal blood flow (GMBF), and glandular mucosal damage were studied in anesthetized rats. Ethanol administration decreased gastric acid secretion and GMBF, which were accompanied by a marked increase in gastric mucosal damage. Acute nicotine incubation 2 or 4 mg dose-dependently elevated both the titratable acid in the luminal solution and the gastric secretory volume; it also prevented the depressive action on GMBF and gastric mucosal damage in ethanol-treated animals. Chronic nicotine treatment for 10 days reduced the inhibitory action of ethanol on gastric acid secretion; the higher dose (25 micrograms/ml drinking water) potentiated the decrease of GMBF and the ulcerogenic property of ethanol. However, chronic treatment with the lower dose (5 micrograms/ml drinking water) had the opposite effects; it also markedly increased the gastric secretory volume. It is concluded that acute nicotine pretreatment elevates, whereas chronic nicotine pretreatment differentially affects GMBF. These effects could account for their protective or preventive actions on ethanol ulceration. The increase in nonacid gastric secretory volume by nicotine could partially explain its antiulcer effect. Furthermore, the acid secretory state of the stomach appears unrelated to the ulcerogenic property of ethanol. PMID:2295286

  15. Regulation of nicotinic receptors in rat brain following quasi-irreversible nicotinic blockade by chlorisondamine and chronic treatment with nicotine.

    PubMed Central

    el-Bizri, H; Clarke, P B

    1994-01-01

    1. Chronic administration of nicotinic agonists in vivo increases the density of brain nicotinic binding sites. It has been proposed that this up-regulation results from agonist-induced functional blockade of nicotinic receptors. This hypothesis was tested by examining post mortem [3H]-nicotine and [125I]-alpha-bungarotoxin ([125I]-alpha BTX) binding following treatment in vivo with the quasi-irreversible and insurmountable CNS nicotinic blocker chlorisondamine, given either alone or in combination with chronic nicotine administration. 2. In rats that had not received chlorisondamine pretreatment, chronic nicotine administration (0.6 mg kg-1 s.c., twice daily for 12 days) increased [3H]-nicotine binding density (Bmax) in forebrain tissue sections by 19%, with no change in the apparent dissociation constant (KD). Chlorisondamine (10 mg kg-1, s.c.), given once prior to the chronic treatment phase, neither increased [3H]-nicotine binding by itself, nor altered the extent of nicotine-induced up-regulation. Nevertheless, chlorisondamine pretreatment resulted in a persistent blockade of CNS nicotinic receptors, as demonstrated by complete block of acute locomotor responses to nicotine. 3. In a second experiment, [3H]-nicotine and [125I]-alpha BTX binding was measured in tissue homogenates prepared from several brain regions. In the absence of chlorisondamine pretreatment, chronic nicotine administration (1 mg kg-1 s.c., twice daily for 12 days) increased the Bmax of [3H]-nicotine binding in the cerebral cortex (by 34%), striatum (by 28%), midbrain (by 16%) and hippocampus (by 36%); KD was unchanged. As before, this up-regulation was neither mimicked nor blocked by chlorisondamine pretreatment (10 mg kg-1, s.c., given twice), despite persistent blockade of acute locomotor responses to nicotine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7858886

  16. The ternary system K2SO4MgSO4CaSO4

    USGS Publications Warehouse

    Rowe, J.J.; Morey, G.W.; Silber, C.C.

    1967-01-01

    Melting and subsolidus relations in the system K2SO4MgSO4CaSO4 were studied using heating-cooling curves, differential thermal analysis, optics, X-ray diffraction at room and high temperatures and by quenching techniques. Previous investigators were unable to study the binary MgSO4CaSO4 system and the adjacent area in the ternary system because of the decomposition of MgSO4 and CaSO4 at high temperatures. This problem was partly overcome by a novel sealed-tube quenching method, by hydrothermal synthesis, and by long-time heating in the solidus. As a result of this study, we found: (1) a new compound, CaSO4??3MgSO4 (m.p. 1201??C) with a field extending into the ternary system; (2) a high temperature form of MgSO4 with a sluggishly reversible inversion. An X-ray diffraction pattern for this polymorphic form is given; (3) the inversion of ??-CaSO4 (anhydrite) to ??-CaSO4 at 1195??C, in agreement with grahmann; (1) (4) the melting point of MgSO4 is 1136??C and that of CaSO4 is 1462??C (using sealed tube methods to prevent decomposition of the sulphates); (5) calcium langbeinite (K2SO4??2CaSO4) is the only compound in the K2SO4CaSO4 binary system. This resolved discrepancies in the results of previous investigators; (6) a continuous solid solution series between congruently melting K2SOP4??2MgSO4 (langbeinite) and incongruently melting K2SO4??2CaSO4 (calcium langbeinite); (7) the liquidus in the ternary system consists of primary phase fields of K2SO4, MgSO4, CaSO4, langbeinite-calcium langbeinite solid solution, and CaSO4??3MgSO4. The CaSO4 field extends over a large portion of the system. Previously reported fields for the compounds (K2SO4??MgSO4??nCaSO4), K2SO4??3CaSO4 and K2SO4??CaSO4 were not found; (8) a minimum in the ternary system at: 740??C, 25% MgSO4, 6% CaSO4, 69% K2SO4; and ternary eutectics at 882??C, 49% MgSO4, 19% CaSO4, 32% K2SO4; and 880??, 67??5% MgSO4, 5% CaSO4, 27??5% K2SO4. ?? 1967.

  17. Nicotine vaccines to treat tobacco dependence

    PubMed Central

    Goniewicz, Maciej L.; Delijewski, Marcin

    2013-01-01

    Tobacco smoking is globally far more widespread than use of any other substance of abuse. Nicotine is an important tobacco constituent that is responsible for addictive properties of smoking. The currently available medications for the treatment of nicotine addiction have limited efficacy. A challenging novel therapeutic concept is vaccination against nicotine. An efficient vaccine would generate antibodies that sequester nicotine in the blood and prevent its access to the brain. The vaccine would have great potential for treating nicotine addiction and for relapse prevention. We reviewed the current status of vaccines against nicotine addiction that are undergoing clinical trials or are in preclinical development. We discuss problems associated with the development of nicotine vaccines, their efficacy in addiction treatment, challenges and ethical concerns. Existing evidence indicates that nicotine vaccination is well tolerated and capable of inducing an immune response but its effectiveness in increasing smoking abstinence has not been shown so far. PMID:23108361

  18. Melatonin 4 mg as prophylactic therapy for primary headaches: a pilot study

    PubMed Central

    Bougea, Anastasia; Spantideas, Nikolaos; Lyras, Vasilis; Avramidis, Theodoros; Thomaidis, Thomas

    2016-01-01

    Summary There is growing evidence that headaches are connected to melatonin secretion. Our aim was to assess the potential effectiveness of melatonin for primary headache prevention. Forty-nine patients (37 with migraine and 12 with chronic tension-type headache, TTH) were prescribed oral melatonin, 4 mg, 30 minutes before bedtime for six months. Forty-one (83.6%) of the 49 patients completed the study, while eight dropped out for personal reasons. A statistically significant reduction in headache frequency was found between baseline and final follow-up after six months of treatment (p=0.033 for TTH patients and p<0.001 for migraineurs). The Headache Impact Test score was significantly reduced in both groups of headache patients (p=0.002 and p<0.001, respectively). At baseline, melatonin levels, measured both during a headache attack and a pain-free period, did not differ between patients with TTH and migraineurs (p=0.539 and p=0.693, respectively), and no statistically significant differences in Hamilton Depression Rating Scale scores were found between the two groups. This pilot study shows promising results, in terms of headache frequency reduction and daily quality of life improvement, in both groups. PMID:27027892

  19. Cognitive Function During Nicotine Withdrawal: Implications for Nicotine Dependence Treatment

    PubMed Central

    Ashare, Rebecca L.; Falcone, Mary; Lerman, Caryn

    2013-01-01

    Nicotine withdrawal is associated with deficits in neurocognitive function including sustained attention, working memory, and response inhibition. Several convergent lines of evidence suggest that these deficits may represent a core dependence phenotype and a target for treatment development efforts. A better understanding of the mechanisms underlying withdrawal-related cognitive deficits may lead to improve nicotine dependence treatment. We begin with an overview of the neurocognitive effects of withdrawal in rodent and human models, followed by discussion of the neurobehavioral mechanisms that are thought to underlie these effects. We then review individual differences in withdrawal-related neurocognitive effects including genetics, gender, and psychiatric comorbidity. We conclude with a discussion of the implications of this research for developing improved therapies, both pharmacotherapy and behavioral treatments, that target cognitive symptoms of nicotine withdrawal. PMID:23639437

  20. Efficacy and tolerability of an ectoine mouth and throat spray compared with those of saline lozenges in the treatment of acute pharyngitis and/or laryngitis: a prospective, controlled, observational clinical trial.

    PubMed

    Müller, Dörte; Lindemann, Torben; Shah-Hosseini, Kija; Scherner, Olaf; Knop, Markus; Bilstein, Andreas; Mösges, Ralph

    2016-09-01

    The aim of this observational trial was to evaluate the efficacy and tolerability of a mouth and throat spray containing ectoine in the treatment of acute pharyngitis and/or laryngitis. The outcome was compared with control treatment using saline lozenges. This study was designed as a prospective, controlled, non-randomized, observational multicenter clinical trial and was conducted in Germany. The study population consisted of 95 patients. The decision for treatment with either spray or lozenges was based on the patients' preference for pharyngeal or oral application. Investigators assessed symptoms specific to acute pharyngitis/laryngitis and determined the pharyngitis symptom score. Both patients and investigators evaluated the tolerability and efficacy of the treatment applied. Treatment with the spray showed higher efficacy, 1.95 ± 0.81 versus 1.68 ± 0.67 (investigators) and 1.97 ± 0.88 versus 1.57 ± 0.69 (patients, p < 0.05). Treatment with the spray resulted in significantly greater reduction of cervical lymph node swelling (p < 0.05), ∆ spray = 0.44 ± 0.62, ∆ lozenges = 0.21 ± 0.62. The lozenges showed some advantage in relieving cough, ∆ lozenges = 0.62 ± 0.94 versus ∆ spray = 0.44 ± 0.85. Both patients and investigators rated the tolerability of both medical devices as "good" to "very good". Adverse events of mild to moderate severity were either possibly related or not related to the medical devices used. No serious adverse events occurred. Taken together, while the tolerability was consistent in both treatment groups, the ectoine-based spray showed superior efficacy in treating acute pharyngitis and/or laryngitis. PMID:27126336

  1. 21 CFR 172.310 - Aluminum nicotinate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Aluminum nicotinate. 172.310 Section 172.310 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... Special Dietary and Nutritional Additives § 172.310 Aluminum nicotinate. Aluminum nicotinate may be...

  2. 21 CFR 172.310 - Aluminum nicotinate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Aluminum nicotinate. 172.310 Section 172.310 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... Special Dietary and Nutritional Additives § 172.310 Aluminum nicotinate. Aluminum nicotinate may be...

  3. 21 CFR 172.310 - Aluminum nicotinate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Aluminum nicotinate. 172.310 Section 172.310 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Additives § 172.310 Aluminum nicotinate. Aluminum nicotinate may be safely used as a source of niacin...

  4. 21 CFR 172.310 - Aluminum nicotinate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Aluminum nicotinate. 172.310 Section 172.310 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... Special Dietary and Nutritional Additives § 172.310 Aluminum nicotinate. Aluminum nicotinate may be...

  5. 21 CFR 172.310 - Aluminum nicotinate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Aluminum nicotinate. 172.310 Section 172.310 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... Special Dietary and Nutritional Additives § 172.310 Aluminum nicotinate. Aluminum nicotinate may be...

  6. 27 CFR 21.119 - Nicotine solution.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Nicotine solution. 21.119....119 Nicotine solution. (a) Composition. Five gallons of an aqueous solution containing 40 percent nicotine; 3.6 avoirdupois ounces of methylene blue, U.S.P.; water sufficient to make 100 gallons. (b)...

  7. 27 CFR 21.119 - Nicotine solution.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Nicotine solution. 21.119....119 Nicotine solution. (a) Composition. Five gallons of an aqueous solution containing 40 percent nicotine; 3.6 avoirdupois ounces of methylene blue, U.S.P.; water sufficient to make 100 gallons. (b)...

  8. 27 CFR 21.119 - Nicotine solution.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Nicotine solution. 21.119....119 Nicotine solution. (a) Composition. Five gallons of an aqueous solution containing 40 percent nicotine; 3.6 avoirdupois ounces of methylene blue, U.S.P.; water sufficient to make 100 gallons. (b)...

  9. 27 CFR 21.119 - Nicotine solution.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Nicotine solution. 21.119....119 Nicotine solution. (a) Composition. Five gallons of an aqueous solution containing 40 percent nicotine; 3.6 avoirdupois ounces of methylene blue, U.S.P.; water sufficient to make 100 gallons. (b)...

  10. 27 CFR 21.119 - Nicotine solution.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Nicotine solution. 21.119....119 Nicotine solution. (a) Composition. Five gallons of an aqueous solution containing 40 percent nicotine; 3.6 avoirdupois ounces of methylene blue, U.S.P.; water sufficient to make 100 gallons. (b)...

  11. The Serotonin 2C Receptor Agonist Lorcaserin Attenuates Intracranial Self-Stimulation and Blocks the Reward-Enhancing Effects of Nicotine.

    PubMed

    Zeeb, Fiona D; Higgins, Guy A; Fletcher, Paul J

    2015-07-15

    Lorcaserin, a serotonin (5-hydroxytryptamine, 5-HT) 2C receptor agonist, was recently approved for the treatment of obesity. We previously suggested that 5-HT2C receptor agonists affect reward processes and reduce the rewarding effects of drugs of abuse. Here, we determined whether lorcaserin (1) decreases responding for brain stimulation reward (BSR) and (2) prevents nicotine from enhancing the efficacy of BSR. Rats were trained on the intracranial self-stimulation (ICSS) paradigm to nosepoke for BSR of either the dorsal raphé nucleus or left medial forebrain bundle. In Experiment 1, lorcaserin (0.3-1.0 mg/kg) dose-dependently reduced the efficacy of BSR. This effect was blocked by prior administration of the 5-HT2C receptor antagonist SB242084. In Experiment 2, separate groups of rats received saline or nicotine (0.4 mg/kg) for eight sessions prior to testing. Although thresholds were unaltered in saline-treated rats, nicotine reduced reward thresholds. An injection of lorcaserin (0.3 mg/kg) prior to nicotine prevented the reward-enhancing effect of nicotine across multiple test sessions. These results demonstrated that lorcaserin reduces the rewarding value of BSR and also prevents nicotine from facilitating ICSS. Hence, lorcaserin may be effective in treating psychiatric disorders, including obesity and nicotine addiction, by reducing the value of food or drug rewards. PMID:25781911

  12. Nicotine modulation of adolescent dopamine receptor signaling and hypothalamic peptide response.

    PubMed

    Mojica, Celina Y; Dao, Jasmin M; Yuan, Menglu; Loughlin, Sandra E; Leslie, Frances M

    2014-02-01

    Adolescence is a sensitive developmental period for limbic and dopamine systems that coincides with the typical age for onset of tobacco use. We have previously shown that a 4-day, low-dose nicotine (0.06 mg/kg) pretreatment enhances locomotor and penile response to the D2-like agonist, quinpirole (0.4 mg/kg), in adolescent but not adult rats. The present study is designed to determine mechanisms underlying this effect. Nicotine enhancement of adolescent quinpirole-induced locomotion was mediated by D2 receptors (D2Rs) since it was blocked by the D2R antagonist, L-741,626, but not by the D3R and D4R antagonists, NGB 2904 and L-745,870. Enhancement of quinpirole-induced erectile response was blocked by both L-741,626 and NGB 2904, indicating involvement of D3Rs. Whereas D2R binding was unaffected by adolescent nicotine pretreatment, effector coupling in the striatum was increased, as determined by GTPγS binding. Nicotine pretreatment enhanced quinpirole-induced c-fos mRNA expression in the hypothalamic paraventricular and supraoptic nuclei in adolescents only. Adolescent nicotine pretreatment enhanced c-fos mRNA expression in corticotropin releasing factor (CRF) cells of the paraventricular nucleus, and enhancement of penile erection was blocked by the CRF-1 receptor antagonist, CP 376,396. These findings suggest that adolescent dopamine and CRF systems are vulnerable to alteration by nicotine. This is the first evidence for a role of CRF in adolescent erectile response. PMID:24157491

  13. Nicotinic acetylcholine receptors and cancer

    PubMed Central

    DANG, NINGNING; MENG, XIANGUANG; SONG, HAIYAN

    2016-01-01

    Nicotine, the primary addictive constituent of cigarettes, is believed to contribute to cancer promotion and progression through the activation of nicotinic acetylcholine receptors (nAChRs), which are membrane ligand-gated cation channels. nAChRs activation can be triggered by the neurotransmitter Ach, or certain other biological compounds, such as nicotine. In recent years, genome-wide association studies have indicated that allelic variation in the α5-α3-β4 nAChR cluster on chromosome 15q24-15q25.1 is associated with lung cancer risk. The role of nAChRs in other types of cancer has also been reported. The present review highlights the role of nAChRs in types of human cancer. PMID:27123240

  14. Nicotine Exposure during Adolescence Enhances Behavioral Sensitivity to Nicotine during Adulthood in Wistar Rats

    PubMed Central

    Bracken, Amy L.; Chambers, R. Andrew; Berg, Sarah A.; Rodd, Zachary A.; McBride, William J.

    2011-01-01

    Rationale Drug use during adolescence is associated with an increased propensity for drug dependency during adulthood. Therefore, the effects of adolescent exposure to nicotine on adult behavioral responsiveness to nicotine are of particular importance. Objectives The objective of the current study was to determine if adolescent nicotine exposure would enhance behavioral sensitivity and development of sensitization to nicotine during adulthood. Materials and Methods Male Wistar rats were assigned to one of three groups that received subcutaneous (s.c.) injections of nicotine (0, 0.25, or 0.5 mg/kg) in the home cage for 12 consecutive days during adolescence, PD 31–42. Starting on PD 80, distance traveled, rearing, and stereotypy were recorded in locomotor activity chambers each day for 10 days, following s.c. injections of 0, 0.25, or 0.5 mg/kg nicotine. One week later, a final challenge session took place during which rats were injected with 0.5 mg/kg nicotine. Results Rats exposed to nicotine during adolescence displayed a greater locomotor response to a novel environment than saline-treated rats. Adolescent nicotine treatment also resulted in context-independent sensitization to the acute locomotor activating properties of nicotine, including distance traveled and stereotypy, as measured on the first day of adulthood nicotine exposure. Adolescent nicotine-treated rats displayed increased sensitivity to repeated nicotine exposures during adulthood, compared to adolescent saline-treated rats, as measured by distance traveled, rearing, and stereotypic behaviors. Finally, rats treated with nicotine only during adolescence were more sensitive to a final nicotine challenge during adulthood than rats treated with nicotine only previously during adulthood. Conclusions Overall, the results suggest that adolescent nicotine treatment predisposes adult rats to develop increased behavioral sensitivity to chronic nicotine treatment and to be more sensitive to the initial

  15. Electronic Nicotine Delivery Systems

    PubMed Central

    Adkison, Sarah E.; O’Connor, Richard J.; Bansal-Travers, Maansi; Hyland, Andrew; Borland, Ron; Yong, Hua-Hie; Cummings, K. Michael; McNeill, Ann; Thrasher, James F.; Hammond, David; Fong, Geoffrey T.

    2013-01-01

    Background Electronic nicotine delivery systems (ENDS) initially emerged in 2003 and have since become widely available globally, particularly over the Internet. Purpose Data on ENDS usage patterns are limited. The current paper examines patterns of ENDS awareness, use, and product-associated beliefs among current and former smokers in four countries. Methods Data come from Wave 8 of the International Tobacco Control Four-Country Survey, collected July 2010 to June 2011 and analyzed through June 2012. Respondents included 5939 current and former smokers in Canada (n=1581); the U.S. (n=1520); the United Kingdom (UK; n=1325); and Australia (n=1513). Results Overall, 46.6% were aware of ENDS (U.S.: 73%, UK: 54%, Canada: 40%, Australia: 20%); 7.6% had tried ENDS (16% of those aware of ENDS); and 2.9% were current users (39% of triers). Awareness of ENDS was higher among younger, non-minority smokers with higher incomes who were heavier smokers. Prevalence of trying ENDS was higher among younger, nondaily smokers with a high income and among those who perceived ENDS as less harmful than traditional cigarettes. Current use was higher among both nondaily and heavy (≥20 cigarettes per day) smokers. In all, 79.8% reported using ENDS because they were considered less harmful than traditional cigarettes; 75.4% stated that they used ENDS to help them reduce their smoking; and 85.1% reported using ENDS to help them quit smoking. Conclusions Awareness of ENDS is high, especially in countries where they are legal (i.e., the U.S. and UK). Because trial was associated with nondaily smoking and a desire to quit smoking, ENDS may have potential to serve as a cessation aid. PMID:23415116

  16. Discriminative and reinforcing stimulus effects of nicotine, cocaine, and cocaine + nicotine combinations in rhesus monkeys.

    PubMed

    Mello, Nancy K; Newman, Jennifer L

    2011-06-01

    Concurrent cigarette smoking and cocaine use is well documented. However, the behavioral pharmacology of cocaine and nicotine combinations is poorly understood, and there is a need for animal models to examine this form of polydrug abuse. The purpose of this study was twofold: first to assess the effects of nicotine on the discriminative stimulus effects of cocaine, and second, to study self-administration of nicotine/cocaine combinations in a novel polydrug abuse model. In drug discrimination experiments, nicotine increased the discriminative stimulus effects of low cocaine doses in two of three monkeys, but nicotine did not substitute for cocaine in any monkey. Self-administration of cocaine and nicotine alone, and cocaine + nicotine combinations was studied under a second-order fixed ratio 2, variable ratio 16 (FR2[VR16:S]) schedule of reinforcement. Cocaine and nicotine alone were self-administered in a dose-dependent manner. The combination of marginally reinforcing doses of cocaine and nicotine increased drug self-administration behavior above levels observed with the same dose of either cocaine or nicotine alone. These findings indicate that nicotine may increase cocaine's discriminative stimulus and reinforcing effects in rhesus monkeys, and illustrate the feasibility of combining cocaine and nicotine in a preclinical model of polydrug abuse. Further studies of the behavioral effects of nicotine + cocaine combinations will contribute to our understanding the pharmacology of dual nicotine and cocaine dependence, and will be useful for evaluation of new treatment medications. PMID:21480727

  17. Genetics of Nicotine Dependence and Pharmacotherapy

    PubMed Central

    Lessov-Schlaggar, Christina N.; Pergadia, Michele L.; Khroyan, Taline V.; Swan, Gary E.

    2008-01-01

    Nicotine dependence is substantially heritable. Several regions across the genome have been implicated in containing genes that confer liability to nicotine dependence and variation in individual genes has been associated with nicotine dependence. Smoking cessation measures are also heritable, and measured genetic variation is associated with nicotine dependence treatment efficacy. Despite significant strides in the understanding of the relative contribution of genetic and environmental factors to nicotine dependence and treatment, emergent challenges necessitate interdisciplinary coordinated effort for effective problem solving. These challenges include refinement of the nicotine dependence phenotype, better understanding of the dynamic interplay between genes and environment in nicotine dependence etiology, application and development of molecular and statistical methodology that can adequately address vast amounts of data, and continuous translational cross-talk. PMID:17888884

  18. Effect of gaseous ammonia on nicotine sorption

    SciTech Connect

    Webb, A.M.; Singer, B.C.; Nazaroff, W.W.

    2002-06-01

    Nicotine is a major constituent of environmental tobacco smoke. Sorptive interactions of nicotine with indoor surfaces can substantially alter indoor concentrations. The phenomenon is poorly understood, including whether sorption is fully reversible or partially irreversible. They hypothesize that acid-base chemistry on indoor surfaces might contribute to the apparent irreversibility of nicotine sorption under some circumstances. Specifically, they suggest that nicotine may become protonated on surfaces, markedly reducing its vapor pressure. If so, subsequent exposure of the surface to gaseous ammonia, a common base, could raise the surface pH, causing deprotonation and desorption of nicotine from surfaces. A series of experiments was conducted to explore the effect of ammonia on nicotine sorption to and reemission from surfaces. The results indicate that, under some conditions, exposure to gaseous ammonia can substantially increase the rate of desorption of previously sorbed nicotine from common indoor surface materials.

  19. Nicotine: abused substance and therapeutic agent.

    PubMed Central

    Le Houezec, J

    1998-01-01

    Tobacco dependence is a complex phenomenon that is not fully understood. Nicotine is the main alkaloid in tobacco and the addictive compound of tobacco. It can improve both mood and cognitive functioning; these positive effects are strong reinforcements for smokers and contribute to their addiction. Opposite results also have been reported, however, and the effects of nicotine remain controversial. Recent epidemiological and empirical studies have indicated that smoking or nicotine or both may have protective effects against certain diseases. These findings have suggested that nicotine may be used as a therapeutic agent. However, because a variety of nicotinic cholinergic receptors are present in the brain, new agonist compounds may prove to be more effective than nicotine for therapeutic purposes. Studies are reviewed and the suggestion made that nicotine may prove useful as a tool to help us understand normal and pathological brain functioning. PMID:9549250

  20. Racial differences in the relationship between rate of nicotine metabolism and nicotine intake from cigarette smoking.

    PubMed

    Ross, Kathryn C; Gubner, Noah R; Tyndale, Rachel F; Hawk, Larry W; Lerman, Caryn; George, Tony P; Cinciripini, Paul; Schnoll, Robert A; Benowitz, Neal L

    2016-09-01

    Rate of nicotine metabolism has been identified as an important factor influencing nicotine intake and can be estimated using the nicotine metabolite ratio (NMR), a validated biomarker of CYP2A6 enzyme activity. Individuals who metabolize nicotine faster (higher NMR) may alter their smoking behavior to titrate their nicotine intake in order to maintain similar levels of nicotine in the body compared to slower nicotine metabolizers. There are known racial differences in the rate of nicotine metabolism with African Americans on average having a slower rate of nicotine metabolism compared to Whites. The goal of this study was to determine if there are racial differences in the relationship between rate of nicotine metabolism and measures of nicotine intake assessed using multiple biomarkers of nicotine and tobacco smoke exposure. Using secondary analyses of the screening data collected in a recently completed clinical trial, treatment-seeking African American and White daily smokers (10 or more cigarettes per day) were grouped into NMR quartiles so that the races could be compared at the same NMR, even though the distribution of NMR within race differed. The results indicated that rate of nicotine metabolism was a more important factor influencing nicotine intake in White smokers. Specifically, Whites were more likely to titrate their nicotine intake based on the rate at which they metabolize nicotine. However, this relationship was not found in African Americans. Overall there was a greater step-down, linear type relationship between NMR groups and cotinine or cotinine/cigarette in African Americans, which is consistent with the idea that differences in blood cotinine levels between the African American NMR groups were primarily due to differences in CYP2A6 enzyme activity without titration of nicotine intake among faster nicotine metabolizers. PMID:27180107

  1. Nicotine and the Developing Human

    PubMed Central

    England, Lucinda J.; Bunnell, Rebecca E.; Pechacek, Terry F.; Tong, Van T.; McAfee, Tim A.

    2015-01-01

    The elimination of cigarettes and other combusted tobacco products in the U.S. would prevent tens of millions of tobacco-related deaths. It has been suggested that the introduction of less harmful nicotine delivery devices, such as electronic cigarettes or other electronic nicotine delivery systems, will accelerate progress toward ending combustible cigarette use. However, careful consideration of the potential adverse health effects from nicotine itself is often absent from public health debates. Human and animal data support that nicotine exposure during periods of developmental vulnerability (fetal through adolescent stages) has multiple adverse health consequences, including impaired fetal brain and lung development, and altered development of cerebral cortex and hippocampus in adolescents. Measures to protect the health of pregnant women and children are needed and could include (1) strong prohibitions on marketing that increase youth uptake; (2) youth access laws similar to those in effect for other tobacco products; (3) appropriate health warnings for vulnerable populations; (4) packaging to prevent accidental poisonings; (5) protection of non-users from exposure to secondhand electronic cigarette aerosol; (6) pricing that helps minimize youth initiation and use; (7) regulations to reduce product addiction potential and appeal for youth; and (8) the age of legal sale. PMID:25794473

  2. The influence of chronic or acute nicotine pretreatment on ethanol-induced gastric ulceration in the rat.

    PubMed

    Wong, S H; Ogle, C W; Cho, C H

    1986-07-01

    The effects in rats of chronic or acute nicotine pretreatment were studied on three gastric parameters: ethanol-induced ulceration, gastric wall mucus content and gastric acid secretion, under basal or histamine-stimulated conditions. Oral administration of ethanol (40%, 10 ml kg-1) depleted gastric wall mucus and produced ulceration in the gastric glandular mucosa. Ten-day nicotine pretreatment (15 or 25 micrograms ml-1 drinking water) worsened the adverse effects of ethanol on mucosal ulceration and mucus content, potentiated the gastric secretory action of histamine, but did not affect basal acid secretion. Single oral doses of nicotine (2 or 4 mg kg-1, given 1 h beforehand) prevented ulceration and mucus depletion in ethanol-treated animals; however, they did not influence either basal or histamine-stimulated gastric acid output. It is concluded that chronic nicotine administration aggravates ethanol ulceration, possibly by decreasing gastric wall mucus content and sensitizing the stomach to the acid secretory action of histamine. On the other hand, an acute oral dose of nicotine preserves the mucus content and prevents ethanol-induced ulcer formation. PMID:2427681

  3. Effects of alpha-7 nicotinic acetylcholine receptor positive allosteric modulator on lipopolysaccharide-induced neuroinflammatory pain in mice.

    PubMed

    Abbas, Muzaffar; Rahman, Shafiqur

    2016-07-15

    Evidence indicates that microglial activation contributes to the pathophysiology and maintenance of neuroinflammatory pain involving central nervous system alpha-7 nicotinic acetylcholine receptors. The objective of the present study was to determine the effects of 3a,4,5,9b-Tetrahydro-4-(1-naphthalenyl)-3H-cyclopentan[c]quinoline-8-sulfonamide (TQS), an alpha-7 nicotinic acetylcholine receptor positive allosteric modulator (PAM), on tactile allodynia and thermal hyperalgesia following lipopolysaccharide (LPS)-induced microglial activation in hippocampus, a neuroinflammatory pain model in mice. In addition, we examined the effects of TQS on microglial activation marker, an ionized calcium-binding adapter molecule 1 (Iba-1), in the hippocampus may be associated with neuroinflammatory pain. Pretreatment of TQS (4mg/kg) significantly reduced LPS (1mg/kg)-induced tactile allodynia and thermal hyperalgesia. Moreover, pretreatment of methyllycaconitine (3mg/kg) significantly reversed TQS-induced antiallodynic and antihyperalgesic responses indicating the involvement of alpha-7 nicotinic acetylcholine receptor. Pretreatment of TQS significantly decreased LPS-induced increased in hippocampal Iba-1 expression. Overall, these results suggest that TQS reduces LPS-induced neuroinflammatory pain like symptoms via modulating microglial activation likely in the hippocampus and/or other brain region by targeting alpha-7 nicotinic acetylcholine receptor. Therefore, alpha-7 nicotinic acetylcholine receptor PAM such as TQS could be a potential drug candidate for the treatment of neuroinflammatory pain. PMID:27154173

  4. Nitrosamines as nicotinic receptor ligands.

    PubMed

    Schuller, Hildegard M

    2007-05-30

    Nitrosamines are carcinogens formed in the mammalian organism from amine precursors contained in food, beverages, cosmetics and drugs. The potent carcinogen, NNK, and the weaker carcinogen, NNN, are nitrosamines formed from nicotine. Metabolites of the nitrosamines react with DNA to form adducts responsible for genotoxic effects. We have identified NNK as a high affinity agonist for the alpha7 nicotinic acetylcholine receptor (alpha7nAChR) whereas NNN bound with high affinity to epibatidine-sensitive nAChRs. Diethylnitrosamine (DEN) bound to both receptors but with lower affinity. High levels of the alpha7nAChR were expressed in human small cell lung cancer (SCLC) cell lines and in hamster pulmonary neuroendocrine cells (PNECs), which serve as a model for the cell of origin of human SCLC. Exposure of SCLC or PNECs to NNK or nicotine increased expression of the alpha7nAChR and caused influx of Ca(2+), activation of PKC, Raf-1, ERK1/2, and c-myc, resulting in the stimulation of cell proliferation. Signaling via the alpha7nAChR was enhanced when cells were maintained in an environment of 10-15% CO(2) similar to that in the diseased lung. Hamsters with hyperoxia-induced pulmonary fibrosis developed neuroendocrine lung carcinomas similar to human SCLC when treated with NNK, DEN, or nicotine. The development of the NNK-induced tumors was prevented by green tea or theophylline. The beta-adrenergic receptor agonist, isoproterenol or theophylline blocked NNK-induced cell proliferation in vitro. NNK and nicotine-induced hyperactivity of the alpha7nAChR/RAF/ERK1/2 pathway thus appears to play a crucial role in the development of SCLC in smokers and could be targeted for cancer prevention. PMID:17459420

  5. Nicotine Related Brain Activity: The Influence Of Smoking History and Blood Nicotine Levels, an Exploratory Study

    PubMed Central

    Yamamoto, Rinah T.; Rohan, Michael L.; Goletiani, Nathalie; Olson, David; Peltier, MacKenzie; Renshaw, Perry F.; Mello, Nancy K.

    2012-01-01

    OBJECTIVE In this study, we sought to explore brain activity in nicotine-dependent men in response to acute intravenous nicotine using pharmacological magnetic resonance imaging (phMRI). METHODS phMRI was used to evaluate brain activity in response to 1.5 mg/70 kg intravenous nicotine or saline. The nicotine and saline were administered on different visits. The time courses of individual subjects’ nicotine levels were used as regressors to assess neural activity relating to the infusions. The influence of Smoking history and physiological measures on the response to nicotine were also investigated. RESULTS Greater lifetime exposure to cigarette smoking was significantly correlated with higher peak serum nicotine levels. PhMRI analysis of the differential response of nicotine compared to the saline condition showed distinctive activation patterns when analyzed with a) the nicotine time course, b) nicotine time course controlling for smoking history (pack years), and c) pack years controlling for nicotine. CONCLUSIONS These results suggest that smoking exposure history influences serum nicotine levels and the brain’s response to nicotine. Alterations in brain activity may be a result of vascular and neuro-adaptations involved in drug exposure and addiction. PMID:23117126

  6. Pharmacogenetics of nicotine and associated smoking behaviors.

    PubMed

    Tanner, Julie-Anne; Chenoweth, Meghan J; Tyndale, Rachel F

    2015-01-01

    This chapter summarizes genetic factors that contribute to variation in nicotine pharmacokinetics and nicotine's pharmacological action in the central nervous system (CNS), and how this in turn influences smoking behaviors. Nicotine, the major psychoactive compound in cigarette smoke, is metabolized by a number of enzymes, including CYP2A6, CYP2B6, FMOs, and UGTs, among others. Variation in the genes encoding these enzymes, in particular CYP2A6, can alter the rate of nicotine metabolism and smoking behaviors. Faster nicotine metabolism is associated with higher cigarette consumption and nicotine dependence, as well as lower quit rates. Variation in nicotine's CNS targets and downstream signaling pathways can also contribute to interindividual differences in smoking patterns. Binding of nicotine to neuronal nicotinic acetylcholine receptors (nAChRs) mediates the release of several neurotransmitters including dopamine and serotonin. Genetic variation in nAChRs, and in transporter and enzyme systems that leads to altered CNS levels of dopamine and serotonin, is associated with a number of smoking behaviors. To date, the precise mechanism underpinning many of these findings remains unknown. Considering the complex etiology of nicotine addiction, a more comprehensive approach that assesses the contribution of multiple gene variants, and their interaction with environmental factors, will likely improve personalized therapeutic approaches and increase smoking cessation rates. PMID:25655887

  7. Characteristics of conditioned taste aversion produced by nicotine in rats.

    PubMed Central

    Kumar, R.; Pratt, J. A.; Stolerman, I. P.

    1983-01-01

    1 Nicotine produced conditioned taste aversions in rats which were directly related to the dose of nicotine and to the number of conditioning trials. 2 The tobacco alkaloid (-)-nicotine was four to five times as potent as its stereoisomer, (+)-nicotine. 3 Mecamylamine but not hexamethonium blocked the development of taste aversions produced by nicotine. 4 Mecamylamine did not block the development of taste aversions produced by apomorphine. 5 Prolonged treatment with mecamylamine prior to conditioning did not produce supersensitivity to nicotine. PMID:6135477

  8. Nicotinic Cholinergic Synaptic Mechanisms in the Ventral Tegmental Area Contribute to Nicotine Addiction

    ERIC Educational Resources Information Center

    Pidoplichko, Volodymyr I.; Noguchi, Jun; Areola, Oluwasanmi O.; Liang, Yong; Peterson, Jayms; Zhang, Tianxiang; Dani, John A.

    2004-01-01

    Tobacco use is a major health problem that is estimated to cause 4 million deaths a year worldwide. Nicotine is the main addictive component of tobacco. It acts as an agonist to activate and desensitize nicotinic acetylcholine receptors (nAChRs). A component of nicotine's addictive power is attributable to actions on the mesolimbic dopaminergic…

  9. New mechanisms and perspectives in nicotine withdrawal

    PubMed Central

    Jackson, K.J.; Muldoon, P.P.; De Biasi, M.; Damaj, M.I.

    2014-01-01

    Diseases associated with tobacco use constitute a major health problem worldwide. Upon cessation of tobacco use, an unpleasant withdrawal syndrome occurs in dependent individuals. Avoidance of the negative state produced by nicotine withdrawal represents a motivational component that promotes continued tobacco use and relapse after smoking cessation. With the modest success rate of currently available smoking cessation therapies, understanding mechanisms involved in the nicotine withdrawal syndrome are crucial for developing successful treatments. Animal models provide a useful tool for examining neuroadaptative mechanisms and factors influencing nicotine withdrawal, including sex, age, and genetic factors. Such research has also identified an important role for nicotinic receptor subtypes in different aspects of the nicotine withdrawal syndrome (e.g., physical vs. affective signs). In addition to nicotinic receptors, the opioid and endocannabinoid systems, various signal transduction pathways, neurotransmitters, and neuropeptides have been implicated in the nicotine withdrawal syndrome. Animal studies have informed human studies of genetic variants and potential targets for smoking cessation therapies. Overall, the available literature indicates that the nicotine withdrawal syndrome is complex, and involves a range of neurobiological mechanisms. As research in nicotine withdrawal progresses, new pharmacological options for smokers attempting to quit can be identified, and treatments with fewer side effects that are better tailored to the unique characteristics of patients may become available. PMID:25433149

  10. Cigarette smoking, nicotine dependence, and treatment.

    PubMed Central

    Sees, K L

    1990-01-01

    Since the 1988 Surgeon General's report on nicotine addiction, more attention is being given to nicotine dependence as a substantial contributing factor in cigarette smokers' inability to quit. Many new medications are being investigated for treating nicotine withdrawal and for assisting in long-term smoking abstinence. Medications alone probably will not be helpful; they should be used as adjuncts in comprehensive smoking abstinence programs that address not only the physical dependence on nicotine but also the psychological dependence on cigarette smoking. PMID:2190425

  11. [Smoking cessation using nicotine gum].

    PubMed

    Schioldborg, P

    1990-04-10

    Smoking cessation in matched groups with (n = 54) versus without (n = 63) nicotine gum took place in order to test the gum with regard to abstinence rate and experienced value. In all, 71% quit smoking, 23% reduced consumption to half, while in 6% there was no change. The frequency was approximately even in the two groups. One month later, 79% of the quitters in the nicotine gum group still remained abstinent, compared with 54% in the control group (p less than 0.05). Six months later these frequencies were reduced to 34% and 20% respectively. Side effects were reported among one third of the users (aching of the jaw, sore throat), while two thirds found the gum useful. These persons found it hard to be without the gum, and that it reduced the craving for tobacco. In other words, it renders smoking cessation more certain. PMID:2333643

  12. Predictors of the nicotine reinforcement threshold, compensation, and elasticity of demand in a rodent model of nicotine reduction policy*

    PubMed Central

    Grebenstein, Patricia E.; Burroughs, Danielle; Roiko, Samuel A.; Pentel, Paul R.; LeSage, Mark G.

    2015-01-01

    Background The FDA is considering reducing the nicotine content in tobacco products as a population-based strategy to reduce tobacco addiction. Research is needed to determine the threshold level of nicotine needed to maintain smoking and the extent of compensatory smoking that could occur during nicotine reduction. Sources of variability in these measures across sub-populations also need to be identified so that policies can take into account the risks and benefits of nicotine reduction in vulnerable populations. Methods The present study examined these issues in a rodent nicotine self- administration model of nicotine reduction policy to characterize individual differences in nicotine reinforcement thresholds, degree of compensation, and elasticity of demand during progressive reduction of the unit nicotine dose. The ability of individual differences in baseline nicotine intake and nicotine pharmacokinetics to predict responses to dose reduction was also examined. Results Considerable variability in the reinforcement threshold, compensation, and elasticity of demand was evident. High baseline nicotine intake was not correlated with the reinforcement threshold, but predicted less compensation and less elastic demand. Higher nicotine clearance predicted low reinforcement thresholds, greater compensation, and less elastic demand. Less elastic demand also predicted lower reinforcement thresholds. Conclusions These findings suggest that baseline nicotine intake, nicotine clearance, and the essential value of nicotine (i.e. elasticity of demand) moderate the effects of progressive nicotine reduction in rats and warrant further study in humans. They also suggest that smokers with fast nicotine metabolism may be more vulnerable to the risks of nicotine reduction. PMID:25891231

  13. Solid Solution Effects on the MgAl2O4-MgGa2O4 System

    SciTech Connect

    O'Hara, Kelley; Smith, Jeffrey D; Hemrick, James Gordon

    2009-01-01

    Phase relations between two spinel compounds (MgAl2O4 and MgGa2O4) were studied. Stoichiometric MgAl2O4 was formed in the laboratory through a coprecipitation method. Complete solid solution formation int eh MgAl2O4-MgGa2O4 systems was confirmed through X-ray diffraction analysis. Solid solution between MgAl2O4-MgGa2O4 decreases thermal conductivity at all temperatures up to 900oC. At 200oC with 10 mol% additoin of MgGa2O4 thermal conductivity decreases approximately 25%, and at 900oC there was still an 8% decrease. Additionally, preliminary studies show that porosity between 5% and 10% does not have an appreciable effect on the thermal conductivity in this study.

  14. Phase Equilibria, Crystal Structure and Hydriding/Dehydriding Mechanism of Nd4Mg80Ni8 Compound

    NASA Astrophysics Data System (ADS)

    Luo, Qun; Gu, Qin-Fen; Zhang, Jie-Yu; Chen, Shuang-Lin; Chou, Kuo-Chih; Li, Qian

    2015-10-01

    In order to find out the optimal composition of novel Nd-Mg-Ni alloys for hydrogen storage, the isothermal section of Nd-Mg-Ni system at 400 °C is established by examining the equilibrated alloys. A new ternary compound Nd4Mg80Ni8 is discovered in the Mg-rich corner. It has the crystal structure of space group I41/amd with lattice parameters of a = b = 11.2743(1) Å and c = 15.9170(2) Å, characterized by the synchrotron powder X-ray diffraction (SR-PXRD). High-resolution transmission electron microscopy (HR-TEM) is used to investigate the microstructure of Nd4Mg80Ni8 and its hydrogen-induced microstructure evolution. The hydrogenation leads to Nd4Mg80Ni8 decomposing into NdH2.61-MgH2-Mg2NiH0.3 nanocomposites, where the high density phase boundaries provide a great deal of hydrogen atoms diffusion channels and nucleation sites of hydrides, which greatly enhances the hydriding/dehydriding (H/D) properties. The Nd4Mg80Ni8 exhibits a good cycle ability. The kinetic mechanisms of H/D reactions are studied by Real Physical Picture (RPP) model. The rate controlling steps are diffusion for hydriding reaction in the temperature range of 100 ~ 350 °C and surface penetration for dehydriding reaction at 291 ~ 347 °C. In-situ SR-PXRD results reveal the phase transformations of Mg to MgH2 and Mg2Ni to Mg2NiH4 as functions of hydrogen pressure and hydriding time.

  15. Phase Equilibria, Crystal Structure and Hydriding/Dehydriding Mechanism of Nd4Mg80Ni8 Compound

    PubMed Central

    Luo, Qun; Gu, Qin-Fen; Zhang, Jie-Yu; Chen, Shuang-Lin; Chou, Kuo-Chih; Li, Qian

    2015-01-01

    In order to find out the optimal composition of novel Nd-Mg-Ni alloys for hydrogen storage, the isothermal section of Nd-Mg-Ni system at 400 °C is established by examining the equilibrated alloys. A new ternary compound Nd4Mg80Ni8 is discovered in the Mg-rich corner. It has the crystal structure of space group I41/amd with lattice parameters of a = b = 11.2743(1) Å and c = 15.9170(2) Å, characterized by the synchrotron powder X-ray diffraction (SR-PXRD). High-resolution transmission electron microscopy (HR-TEM) is used to investigate the microstructure of Nd4Mg80Ni8 and its hydrogen-induced microstructure evolution. The hydrogenation leads to Nd4Mg80Ni8 decomposing into NdH2.61-MgH2-Mg2NiH0.3 nanocomposites, where the high density phase boundaries provide a great deal of hydrogen atoms diffusion channels and nucleation sites of hydrides, which greatly enhances the hydriding/dehydriding (H/D) properties. The Nd4Mg80Ni8 exhibits a good cycle ability. The kinetic mechanisms of H/D reactions are studied by Real Physical Picture (RPP) model. The rate controlling steps are diffusion for hydriding reaction in the temperature range of 100 ~ 350 °C and surface penetration for dehydriding reaction at 291 ~ 347 °C. In-situ SR-PXRD results reveal the phase transformations of Mg to MgH2 and Mg2Ni to Mg2NiH4 as functions of hydrogen pressure and hydriding time. PMID:26471964

  16. Strain localization parameters of AlCu4MgSi processed by high-energy electron beams

    SciTech Connect

    Lunev, A. G. Nadezhkin, M. V.; Konovalov, S. V.; Teresov, A. D.

    2015-10-27

    The influence of the electron beam surface treatment of AlCu4MgSi on the strain localization parameters and on the critical strain value of the Portevin–Le Chatelier effect has been considered. The strain localization parameters were measured using speckle imaging of the specimens subjected to the constant strain rate uniaxial tension at a room temperature. Impact of the surface treatment on the Portevin–Le Chatelier effect has been investigated.

  17. Psychopharmacological interactions between nicotine and ethanol.

    PubMed

    Rose, Jed E; Brauer, Lisa H; Behm, Frederique M; Cramblett, Matthew; Calkins, Kevin; Lawhon, Dawn

    2004-02-01

    Epidemiological, clinical, and laboratory evidence has shown a positive correlation between cigarette smoking and ethanol use, and previous studies suggest some commonality in the neural pathways mediating effects of nicotine and ethanol. In this study, the subjective and behavioral interactions among nicotine, ethanol, and the nicotinic antagonist mecamylamine were investigated. The main objectives were to determine how the rewarding effects of nicotine might be modified by ethanol, and to compare the effects of ethanol with those of a nicotinic antagonist (mecamylamine). A total of 48 smokers who regularly consumed alcoholic beverages participated in four laboratory sessions presenting a 2 (nicotine vs. denicotinized cigarette smoke)x2 (10 mg oral mecamylamine hydrochloride vs. placebo)x2 (ethanol.5 g/kg vs. placebo) design, with ethanol as a between-subjects factor. Dependent measures included blood alcohol concentration (BAC), as assessed by breath alcohol detector; subjective drug effects; and rate of ad lib smoking during a 2-hr period. Results showed that peak BAC averaged.03 g/dl in the ethanol condition. Ethanol potentiated some of the subjective rewarding effects of nicotine, including smoking satisfaction, stimulant as well as calming effects, and relief of craving for cigarettes. During the ad lib smoking period, mecamylamine decreased satisfaction associated with the nicotine-containing cigarettes; mecamylamine also induced smoking but only in the placebo ethanol condition. These results highlight the potent interaction between ethanol and nicotinic systems, and suggest that ethanol can potentiate the rewarding effects of nicotine as well as offset some of the effects of a nicotinic antagonist. PMID:14982697

  18. Response disinhibition evoked by the administration of nicotine and nicotine-associated contextual cues

    PubMed Central

    Kirshenbaum, Ari P.; Johnson, Matthew W.; Schwarz, Sarah L.; Jackson, Eric R.

    2009-01-01

    Nicotine causes dose-dependent alterations in accuracy on the differential-reinforcement of low-rate responding (DRL) 29.5-s schedule in rats. The current investigation evaluated whether nicotine-associated contextual cues can produce nicotine-like perturbations in DRL-schedule performance in the absence of nicotine. Nicotine and saline administrations occurred just prior to DRL 29.5-s schedule responding for sucrose solution, and two different experimental contexts (differentiated by visual, olfactory, and tactile cues) were utilized. All subjects (N = 16) experienced two consecutive daily sessions of DRL-schedule responding per day. The experimental group (n = 8) was exposed to saline immediately prior to the first session and 0.3mg/kg nicotine before the second session, and the context was changed between sessions. This sequence of saline and then nicotine administration, paired with two reliable contexts, persisted for 12 consecutive days and successive nicotine administrations corresponded with increasingly poorer performance on the DRL 29.5-s schedule. No nicotine was administered for days 13–20 during context testing, and the nicotine-associated context produced response disinhibition on the DRL schedule. Two control groups were included in the design; subjects in one control group (n = 4) received saline in each context to verify that the contexts themselves were not exerting control over operant responding. To assess how explicit and non-explicit pairings of nicotine and contextual cues influenced DRL behavior, subjects in a second control group (n = 4) were given nicotine prior to the second session, but the contexts were not altered between sessions. The results from this experiment suggest that environmental stimuli associated with nicotine exposure can come to elicit nicotine-induced performance decrements on a DRL 29.5-s schedule. PMID:19640659

  19. Characterization of SPECTRUM Variable Nicotine Research Cigarettes

    PubMed Central

    Richter, Patricia; Steven, Pappas R.; Bravo, Roberto; Lisko, Joseph G.; Damian, Maria; Gonzalez-Jimenez, Nathalie; Gray, Naudia; Keong, Lisa M.; Kimbrell, Jacob B.; Kuklenyik, Peter; Lawler, Tameka S.; Lee, Grace E.; Mendez, Magaly; Perez, Jose; Smith, Shakia; Tran, Hang; Tyx, Robert; Watson, Clifford H.

    2016-01-01

    Objective To provide researchers an extensive characterization of the SPECTRUM variable nicotine research cigarettes. Methods Data on cigarette physical properties, nicotine content, harmful and potentially harmful constituents in the tobacco filler was compiled. Results Data on physical properties, concentrations of menthol, nicotine and minor alkaloids, tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons, ammonia, and toxic metals in the filler tobacco for all available varieties of Spectrum research cigarettes are provided. The similarity in the chemistry and physical properties of SPECTRUM cigarettes to commercial cigarettes renders them acceptable for use in behavioral studies. Baseline information on harmful and potentially harmful constituents in research tobacco products, particularly constituent levels such as minor alkaloids that fall outside typical ranges reported for commercial, provide researchers with the opportunity to monitor smoking behavior and to identify biomarkers that will inform efforts to understand the role of nicotine in creating and sustaining addiction. Conclusions Well characterized research cigarettes suitable for human consumption are an important tool in clinical studies for investigating the physiological impacts of cigarettes delivering various levels of nicotine, the impact of reduced nicotine cigarettes on nicotine addiction, and the relationship between nicotine dose and smoking behavior. PMID:26779559

  20. Measurement of nicotine in household dust

    SciTech Connect

    Kim, Sungroul Aung, Ther; Berkeley, Emily; Diette, Gregory B.; Breysse, Patrick N.

    2008-11-15

    An analytical method of measuring nicotine in house dust was optimized and associations among three secondhand smoking exposure markers were evaluated, i.e., nicotine concentrations of both house dust and indoor air, and the self-reported number of cigarettes smoked daily in a household. We obtained seven house dust samples from self-reported nonsmoking homes and 30 samples from smoking homes along with the information on indoor air nicotine concentrations and the number of cigarettes smoked daily from an asthma cohort study conducted by the Johns Hopkins Center for Childhood Asthma in the Urban Environment. House dust nicotine was analyzed by isotope dilution gas chromatography-mass spectrometry (GC/MS). Using our optimized method, the median concentration of nicotine in the dust of self-reported nonsmoking homes was 11.7 ng/mg while that of smoking homes was 43.4 ng/mg. We found a substantially positive association (r=0.67, P<0.0001) between house dust nicotine concentrations and the numbers of cigarettes smoked daily. Optimized analytical methods showed a feasibility to detect nicotine in house dust. Our results indicated that the measurement of nicotine in house dust can be used potentially as a marker of longer term SHS exposure.

  1. Nicotine Contamination in Particulate Matter Sampling

    PubMed Central

    Chiu, Yueh-Hsiu; Hart, Jaime E.; Smith, Thomas J.; Hammond, S. Katharine; Garshick, Eric; Laden, Francine

    2009-01-01

    We have addressed potential contamination of PM2.5 filter samples by nicotine from cigarette smoke. We collected two nicotine samples – one nicotine sampling filter was placed inline after the collection of PM2.5 and the other stood alone. The overall correlation between the two nicotine filter levels was 0.99. The nicotine collected on the “stand-alone” filter was slightly greater than that on the “in-line” filter (mean difference = 1.10 μg/m3), but the difference was statistically significant only when PM2.5 was low (≤ 50 μg/m3). It is therefore important to account for personal and secondhand smoke exposure while assessing occupational and environmental PM. PMID:19440403

  2. Effects of Nicotine and Nicotine Expectancy on Attentional Bias for Emotional Stimuli

    PubMed Central

    Adams, Sally; Attwood, Angela S.; Munafò, Marcus R.

    2016-01-01

    Introduction Nicotine’s effects on mood are thought to enhance its addictive potential. However, the mechanisms underlying the effects of nicotine on affect regulation have not been reliably demonstrated in human laboratory studies. We investigated the effects of abstinence (experiment one), and nicotine challenge and expectancy (experiment two) on attentional bias towards facial emotional stimuli differing in emotional valence. Methods In experiment one, 46 nicotine-deprived smokers were randomized to either continue to abstain from smoking or to smoke immediately before testing. In experiment two, 96 nicotine deprived smokers were randomized to smoke a nicotinized or denicotinized cigarette and to be told that the cigarette did or did not contain nicotine. In both experiments participants completed a visual probe task, where positively valenced (happy) and negatively valenced (sad) facial expressions were presented, together with neutral facial expressions. Results In experiment one, there was evidence of an interaction between probe location and abstinence on reaction time, indicating that abstinent smokers showed an attentional bias for neutral stimuli. In experiment two, there was evidence of an interaction between probe location, nicotine challenge and expectation on reaction time, indicating that smokers receiving nicotine, but told that they did not receive nicotine, showed an attentional bias for emotional stimuli. Conclusions Our data suggest that nicotine abstinence appears to disrupt attentional bias towards emotional facial stimuli. These data provide support for nicotine’s modulation of attentional bias as a central mechanism for maintaining affect regulation in cigarette smoking. PMID:25335948

  3. Role of α5-containing nicotinic receptors in neuropathic pain and response to nicotine.

    PubMed

    Xanthos, Dimitris N; Beiersdorf, Johannes W; Thrun, Ariane; Ianosi, Bogdan; Orr-Urtreger, Avi; Huck, Sigismund; Scholze, Petra

    2015-08-01

    Nicotinic receptors in the central nervous system (nAChRs) are known to play important roles in pain processing and modulate behavioral responses to analgesic drugs, including nicotine. The presence of the α5-neuronal nicotinic accessory subunit in the nicotinic receptor complex is increasingly understood to modulate reward and aversive states, addiction, and possibly pathological pain. In the current study, using α5-knockout (KO) mice and subunit-specific antibodies, we assess the role of α5-containing neuronal nicotinic receptors in neuropathic pain and in the analgesic response to nicotine. After chronic constriction injury (CCI) or partial sciatic nerve ligation (PSNL), no differences in mechanical, heat, or cold hyperalgesia were found in wild-type (WT) versus α5-KO littermate mice. The number of α5-containing nAChRs was decreased (rather than increased) after CCI in the spinal cord and in the thalamus. Nevertheless, thermal analgesic response to nicotine was marginally reduced in CCI α5-KO mice at 4 days after CCI, but not at later timepoints or after PSNL. Interestingly, upon daily intermittent nicotine injections in unoperated mice, WT animals developed tolerance to nicotine-induced analgesia to a larger extent than α5-KO mice. Our results suggest that α5-containing nAChRs mediate analgesic tolerance to nicotine but do not play a major role in neuropathic pain. PMID:25725336

  4. Toxicological Analysis of Low-Nicotine and Nicotine-Free Cigarettes

    PubMed Central

    Chen, Jinguo; Higby, Richard; Tian, Defa; Tan, Duanjun; Johnson, Michael D.; Xiao, Yingxian; Kellar, Kenneth J; Feng, Shibao; Shields, Peter G.

    2008-01-01

    Low-nicotine and nicotine-free cigarettes are commercially available under the brand-name Quest®. Some consumers may believe that these are safer cigarettes, and they may smoke more cigarettes or inhale more smoke to compensate for low nicotine yields. Thus, we have studied the toxicological effects of these two cigarettes and compared them with the Kentucky reference cigarette 2R4F. Also, the availability of nicotine-free cigarettes allows for the assessing the role of nicotine in cigarette smoke. In addition to nicotine, some tobacco-specific nitrosamines, aldehydes, and volatile organic compounds were also reduced in the Quest® cigarettes compared to the 2R4F. However, aromatic amines were higher in the nicotine-free compared with low nicotine cigarettes. The Ames test revealed that cigarette smoke condensates from the nicotinefree (CSC-F), low nicotine (CSC-L) and 2R4F (CSC-R) cigarettes had a similar mutagenic potency. Exposure to any CSC caused a similar dose-dependent LDH leakage from normal human bronchial epithelial cells. However, CSC-F had more inhibitory effects on the cell growth than CSC-L and CSC-R. Adding nicotine to the CSC-F attenuated this inhibition. Both Quest® CSCs decreased gap junction intercellular communication and caused cell cycle arrest. CSC exposure increased cytoplasmic nucleosomes, sub-G1/G0 population and apoptotic comet tails. Proapoptotic protein Bax increased independent of p53 induction after exposure to CSC-F. In conclusion, these studies are not consistent with a perception that low-nicotine or nicotine-free cigarettes may have less toxicity in human cells. Nicotine, as it exists in CSC, attenuates cytotoxicity possibly in part through inhibition of apoptotic pathways. PMID:18599178

  5. Nicotine Dependence Reveals Distinct Responses from Neurons and Their Resident Nicotinic Receptors in Medial Habenula.

    PubMed

    Shih, Pei-Yu; McIntosh, J Michael; Drenan, Ryan M

    2015-12-01

    Nicotinic acetylcholine receptors (nAChRs) are the molecular target of nicotine. nAChRs in the medial habenula (MHb) have recently been shown to play a role in nicotine dependence, but it is not clear which nAChR subtypes or MHb neuron types are most important. To identify MHb nAChRs and/or cell types that play a role in nicotine dependence, we studied these receptors and cells with brain slice electrophysiology using both acute and chronic nicotine application. Cells in the ventroinferior (MHbVI) and ventrolateral MHb (MHbVL) subregions expressed functional nAChRs with different pharmacology. Further, application of nicotine to cells in these subregions led to different action potential firing patterns. The latter result was correlated with a differing ability of nicotine to induce nAChR desensitization. Chronic nicotine caused functional upregulation of nAChRs selectively in MHbVI cells, but did not change nAChR function in MHbVL. Importantly, firing responses were also differentially altered in these subregions following chronic nicotine. MHbVI neurons treated chronically with nicotine exhibited enhanced basal pacemaker firing but a blunted nicotine-induced firing response. MHbVL neurons did not change their firing properties in response to chronic nicotine. Together, these results suggest that acute and chronic nicotine differentially affect nAChR function and output of cells in MHb subregions. Because the MHb extensively innervates the interpeduncular nucleus, an area critical for both affective and somatic signs of withdrawal, these results could reflect some of the neurophysiological changes thought to occur in the MHb to the interpeduncular nucleus circuit in human smokers. PMID:26429939

  6. [Nicotine abusing in adult children of alcoholics].

    PubMed

    Suwała, Małgorzata

    2010-01-01

    Adult Children of Alcoholics (ACA) are people who were raised in families abusing alcohol where one of the parents (or both) was addicted to alcohol and where alcohol was the main problem affecting all areas of life. It is estimated that in Poland adult population consists of ACA in 35-40%. Those people represent higher risk of addiction to psychoactive substances, most of all alcohol, but also nicotine. Higher addiction propensity among ACA is a result of their personality's features consisting so called "ACA syndrome". The goal of the study was to determine nicotine addiction frequency and assessment of self-propensity to addiction in chosen ACA group, gathered in three abstinent clubs for alcoholics in Warsaw. Nicotine addiction frequency among the study group members was 58.4% and alcohol addiction frequency was 21.2%. Strong nicotine addiction represented 49.2% of smokers. Men more often than women were addicted to nicotine (0.67 vs. 0.52), on the other hand women were more often than men alcohol addicts (0.18 vs. 0.15). All smokers and nicotine addicts (assessment by HIS test) were aware of their addiction. In relation to initial addiction diagnosis by CAGE test regarded higher percentage of people than it resulted from study group self-assessment (21.2% vs. 16.8). Professional psychotherapy for ACA did not influence substantially the nicotine addiction frequency in the study group. PMID:21360917

  7. The genetics of nicotine dependence.

    PubMed

    Li, Ming D

    2006-04-01

    Despite almost two decades of intensive tobacco-control efforts, approximately 23% of American adults continue to smoke, and 13% are nicotine-dependent. Cigarette smoking is the greatest preventable cause of cancer, accounting for at least 30% of all cancer deaths and 87% of lung cancer deaths. Smoking behavior is influenced by both genetic and environmental factors. Many years of twin and adoption studies have demonstrated that the heritability of liability for nicotine dependence (ND) is at least 50%. During the past several years, significant efforts have been made to identify susceptibility genes for ND using both genome-wide linkage and association analysis approaches. It is expected that identification of susceptibility genes for ND will allow the development and tailoring of both prevention strategies for individuals at risk and effective treatment programs and medicines for individuals who use tobacco products. This review summarizes the recent progress in genetic studies of ND. As genotyping technology is being improved and well-characterized clinical samples on smoking behavior become available, more and more genes and genetic variants responsible for ND will be identified in the near future. PMID:16539894

  8. Nicotinic receptors in addiction pathways.

    PubMed

    Leslie, Frances M; Mojica, Celina Y; Reynaga, Daisy D

    2013-04-01

    Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that consist of pentameric combinations of α and β subunits. These receptors are widely distributed throughout the brain and are highly expressed in addiction circuitry. The role of nAChRs in regulating neuronal activity and motivated behavior is complex and varies both in and among brain regions. The rich diversity of central nAChRs has hampered the characterization of their structure and function with use of classic pharmacological techniques. However, recent molecular approaches using null mutant mice with specific regional lentiviral re-expression, in combination with neuroanatomical and electrophysiological techniques, have allowed the elucidation of the influence of different nAChR types on neuronal circuit activity and behavior. This review will address the influence of nAChRs on limbic dopamine circuitry and the medial habenula-interpeduncular nucleus complex, which are critical mediators of reinforced behavior. Characterization of the mechanisms underlying regulation of addiction pathways by endogenous cholinergic transmission and by nicotine may lead to the identification of new therapeutic targets for treating tobacco dependence and other addictions. PMID:23247824

  9. Role of α5 Nicotinic Acetylcholine Receptors in Pharmacological and Behavioral Effects of Nicotine in Mice

    PubMed Central

    Marks, M. J.; Vann, R. E.; Chen, X.; Gamage, T. F.; Warner, J. A.; Damaj, M. I.

    2010-01-01

    Incorporation of the α5 nicotinic acetylcholine receptor (nAChR) subunit can greatly influence nAChR function without altering receptor number. Although few animal studies have assessed the role of the α5 nAChR in nicotine-mediated behaviors, recent evidence suggests an association between polymorphisms in the α5 nAChR gene and nicotine dependence phenotypes in humans. Thus, additional studies are imperative to elucidate the role and function of the α5 nAChR subunit in nicotine dependence. Using α5(−/−) mice, the current study aimed to examine the role of α5 nAChRs in the initial pharmacological effects of nicotine, nicotine reward using the conditioned place preference model, and the discriminative effects of nicotine using a two-lever drug discrimination model. 86Rb+ efflux and 125I-epibatidine binding assays were conducted to examine the effect of α5 nAChR subunit deletion on expression and activity of functional nAChRs. Results show that α5(−/−) mice are less sensitive to the initial effects of nicotine in antinociception, locomotor activity, and hypothermia measures and that the α5 nAChR is involved in nicotine reward. Alternatively, α5(−/−) mice did not differ from wild-type littermates in sensitivity to the discriminative stimulus effects of nicotine. Furthermore, deletion of the α5 nAChR subunit resulted in a statistically significant decrease in function in the thalamus and hindbrain, but the decreases noted in spinal cord were not statistically significant. Receptor number was unaltered in all areas tested. Taken together, results of the study suggest that α5 nAChRs are involved in nicotine-mediated behaviors relevant to development of nicotine dependence. PMID:20400469

  10. Tobacco/Nicotine and Endogenous Brain Opioids

    PubMed Central

    Xue, Yue; Domino, Edward F.

    2008-01-01

    Smoking is a major public health problem with devastating health consequences. Although many cigarette smokers are able to quit, equal numbers of others cannot! Standard medications to assist in smoking cessation, such as nicotine replacement therapies and bupropion, are ineffective in many remaining smokers. Recent developments in the neurobiology of nicotine dependence have identified several neurotransmitter systems that may contribute to the process of smoking maintenance and relapse. These include: especially dopamine, but also norepinephrine, 5-hydroxytryptamine, acetylcholine, endogenous opioids, gamma-aminobutyric acid (GABA), glutamate, and endocannabinoids. The present review examines the limited contribution of the endogenous opioid system to the complex effects of nicotine/tobacco smoking. PMID:18215788

  11. Electrical stimulation of the insular region attenuates nicotine-taking and nicotine-seeking behaviors.

    PubMed

    Pushparaj, Abhiram; Hamani, Clement; Yu, Wilson; Shin, Damian S; Kang, Bin; Nobrega, José N; Le Foll, Bernard

    2013-03-01

    Pharmacological inactivation of the granular insular cortex is able to block nicotine-taking and -seeking behaviors in rats. In this study, we explored the potential of modulating activity in the insular region using electrical stimulation. Animals were trained to self-administer nicotine (0.03 mg/kg per infusion) under a fixed ratio-5 (FR-5) schedule of reinforcement followed by a progressive ratio (PR) schedule. Evaluation of the effect of stimulation in the insular region was performed on nicotine self-administration under FR-5 and PR schedules, as well on reinstatement of nicotine-seeking behavior induced by nicotine-associated cues or nicotine-priming injections. The effect of stimulation was also examined in brain slices containing insular neurons. Stimulation significantly attenuated nicotine-taking, under both schedules of reinforcement, as well as nicotine-seeking behavior induced by cues and priming. These effects appear to be specific to nicotine-associated behaviors, as stimulation did not have any effect on food-taking behavior. They appear to be anatomically specific, as stimulation surrounding the insular region had no effect on behavior. Stimulation of brain slices containing the insular region was found to inactivate insular neurons. Our results suggest that deep brain stimulation to modulate insular activity should be further explored. PMID:23249816

  12. The effects of chronic versus acute desipramine on nicotine withdrawal and nicotine self-administration in the rat

    PubMed Central

    Paterson, Neil E.; Semenova, Svetlana; Markou, Athina

    2008-01-01

    Rationale Nicotine withdrawal is characterized by depression-like symptomatology that may be mediated by dysregulations in norepinephrine transmission. These aversive aspects of nicotine withdrawal and the rewarding effects of nicotine play major roles in maintaining nicotine dependence. Objectives To evaluate the effects of desipramine (DMI), a preferential norepinephrine reuptake inhibitor and antidepressant, on preclinical models of nicotine dependence in rats. Methods A rate-independent current-intensity discrete-trial threshold intracranial self-stimulation procedure was used to assess brain reward function during nicotine withdrawal induced by cessation of nicotine infusion via subcutaneous osmotic minipumps (3.16 mg/kg/day, base). Nicotine withdrawal was also measured by somatic signs of withdrawal. DMI was administered acutely (2 or 5 mg/kg, salt) during nicotine/saline withdrawal. In other naïve rats, chronic DMI treatment via minipump (15 mg/kg/day, salt) began after 7 days of nicotine/saline exposure and continued during administration of nicotine/saline for 14 days and during nicotine/saline withdrawal. Additional rats acquired intravenous nicotine- or food-maintained responding, were prepared with DMI/vehicle-containing minipumps, and self-administered nicotine or food during 12 days of DMI/vehicle exposure. Results Acute DMI administration had no effect on threshold elevations observed in nicotine-withdrawing rats. Chronic DMI administration prevented the reward threshold elevations and the increased somatic signs of nicotine withdrawal. Although chronic DMI significantly decreased nicotine self-administration, it also decreased food-maintained responding. Conclusions The results suggest that norepinephrine reuptake inhibitors may be effective anti-smoking treatments that reduce the anhedonic depression-like and somatic components of nicotine withdrawal, and may alter the rewarding effects of nicotine and food. PMID:18438738

  13. Effect of nicotine on negative affect among more impulsive smokers.

    PubMed

    Doran, Neal; McChargue, Dennis; Spring, Bonnie; VanderVeen, Joe; Cook, Jessica Werth; Richmond, Malia

    2006-08-01

    In the present study, the authors tested the hypothesis that nicotine would provide greater relief from negative affect for more impulsive smokers than for less impulsive smokers. Euthymic adult smokers (N=70) participated in 2 laboratory sessions, during which they underwent a negative mood induction (music + autobiographical memory), then smoked either a nicotinized or de-nicotinized cigarette. Mixed-effects regression yielded a significant Impulsivity x Condition (nicotinized vs. de-nicotinized) x Time interaction. Simple effects analyses showed that heightened impulsivity predicted greater negative affect relief after smoking a nicotinized cigarette but not after smoking a de-nicotinized cigarette. These data suggest that nicotine may be a disproportionately powerful negative reinforcer for highly impulsive smokers, promoting higher levels of nicotine dependence and inhibiting smoking cessation. PMID:16893271

  14. Nicotine addiction among American youth.

    PubMed

    Grabiak, B R

    1996-01-01

    On August 10, 1995, based on the U.S. Food and Drug Administration's 18-month investigation of the role of nicotine in tobacco, President Bill Clinton announced the FDA's proposed rules against the use of tobacco by young people. The FDA's proposed program, which has met opposition from tobacco companies, has two goals: to minimize the easy access that children have to tobacco products and to decrease the effectiveness of the money the industry spends each year marketing and promoting tobacco products to young people. The Society of Otorhinolaryngology and Head-Neck Nurses' 1991 Position Statement recognizes the importance of members discussing social and health consequences of smokeless tobacco use with local school students. Participation in the Through With Chew Campaign, established by the American Academy of Otolaryngology-Head and Neck Surgery in 1989, is an opportunity for SOHN members to show support for the FDA's proposal. PMID:8788361

  15. The role of nicotinic receptor alpha 7 subunits in nicotine discrimination.

    PubMed

    Stolerman, I P; Chamberlain, S; Bizarro, L; Fernandes, C; Schalkwyk, L

    2004-03-01

    The subtypes of nicotinic receptors at which the behavioural effects of nicotine originate are not fully understood. The experiments described here use mice lacking the alpha7 subunit of nicotinic receptors to investigate the role of alpha7-containing receptors in nicotine discrimination. Wild-type and alpha7-knockout mice were trained in a two-lever nicotine discrimination procedure using a tandem schedule of food reinforcement. Mutant mice exhibited baseline rates of lever-pressing as low as 52.2% of rates in wild-type controls (n=21-24). Mutant and wild-type mice acquired discrimination of nicotine (0.4 or 0.8 mg/kg) at a similar rate (n=10-12) and reached similar final levels of accuracy (71.9 +/- 4.4% and 90.8 +/- 3.1% after 60 training sessions for 0.4 and 0.8 mg/kg training doses, respectively, in mutant mice, as compared with 75.0 +/- 6.5% and 87.6 +/- 4.8% for wild types). The genotypes exhibited similar steep dose-response curves for nicotine discrimination. In both genotypes, dose-response curves for mice trained with 0.8 mg/kg of nicotine were displaced three- to four-fold to the right as compared with those for the mice trained with the smaller dose. The predominant effect of nicotine on the overall rate of responding was a reduction at the largest doses tested and there was no difference between the genotypes. The results suggest that nicotinic receptors containing the alpha7 subunit do not contribute to the discriminative stimulus or response-rate-depressant effects of nicotine, although they may regulate baseline rates of operant responding. PMID:14975691

  16. Effects of chronic buspirone treatment on nicotine and concurrent nicotine+cocaine self-administration.

    PubMed

    Mello, Nancy K; Fivel, Peter A; Kohut, Stephen J

    2013-06-01

    Nicotine dependence and cocaine abuse are major public health problems, and most cocaine abusers also smoke cigarettes. An ideal pharmacotherapy would reduce both cigarette smoking and cocaine abuse. Buspirone (Buspar) is a clinically available, non-benzodiazepine anxiolytic medication that acts on serotonin and dopamine systems. In preclinical studies, it reduced cocaine self-administration following both acute and chronic treatment in rhesus monkeys. The present study evaluated the effectiveness of chronic buspirone treatment on self-administration of intravenous (IV) nicotine and IV nicotine+cocaine combinations. Five cocaine-experienced adult rhesus monkeys (Macaca mulatta) were trained to self-administer nicotine or nicotine+cocaine combinations, and food pellets (1 g) during four 1-h daily sessions under a second-order schedule of reinforcement (FR 2 (VR16:S)). Each nicotine+cocaine combination maintained significantly higher levels of drug self-administration than nicotine or cocaine alone (P<0.05-0.001). Buspirone (0.032-0.56 mg/kg/h) was administered IV through one lumen of a double-lumen catheter every 20 min for 23 h each day, for 7-10 consecutive days. Each 7-10-day sequence of buspirone treatment was followed by saline-control treatment for at least 3 days until food- and drug-maintained responding returned to baseline. Buspirone dose-dependently reduced responding maintained by nicotine alone (0.001-0.1 mg/kg/inj; P<0.01) and by nicotine (0.001 or 0.0032 mg/kg/inj)+cocaine combinations (0.0032 mg/kg/inj; P<0.05-0.001) with no significant effects on food-maintained responding. We conclude that buspirone selectively attenuates the reinforcing effects of nicotine alone and nicotine+cocaine polydrug combinations in a nonhuman primate model of drug self-administration. PMID:23337868

  17. α4β2 nicotinic acetylcholine receptors on dopaminergic neurons mediate nicotine reward and anxiety relief.

    PubMed

    McGranahan, Tresa M; Patzlaff, Natalie E; Grady, Sharon R; Heinemann, Stephen F; Booker, T K

    2011-07-27

    Nicotine is the primary psychoactive substance in tobacco, and it exerts its effects by interaction with various subtypes of nicotinic acetylcholine receptors (nAChRs) in the brain. One of the major subtypes expressed in brain, the α4β2-nAChR, endogenously modulates neuronal excitability and thereby, modifies certain normal as well as nicotine-induced behaviors. Although α4-containing nAChRs are widely expressed across the brain, a major focus has been on their roles within midbrain dopaminergic regions involved in drug addiction, mental illness, and movement control in humans. We developed a unique model system to examine the role of α4-nAChRs within dopaminergic neurons by a targeted genetic deletion of the α4 subunit from dopaminergic neurons in mice. The loss α4 mRNA and α4β2-nAChRs from dopaminergic neurons was confirmed, as well as selective loss of α4β2-nAChR function from dopaminergic but not GABAergic neurons. Two behaviors central to nicotine dependence, reward and anxiety relief, were examined. α4-nAChRs specifically on dopaminergic neurons were demonstrated to be necessary for nicotine reward as measured by nicotine place preference, but not for another drug of addiction, cocaine. α4-nAChRs are necessary for the anxiolytic effects of nicotine in the elevated plus maze, and elimination of α4β2-nAChRs specifically from dopaminergic neurons decreased sensitivity to the anxiolytic effects of nicotine. Deletion of α4-nAChRs specifically from dopaminergic neurons also increased sensitivity to nicotine-induced locomotor depression; however, nicotine-induced hypothermia was unaffected. This is the first work to develop a dopaminergic specific deletion of a nAChR subunit and examine resulting changes in nicotine-related behaviors. PMID:21795541

  18. alpha4beta2 nicotinic acetylcholine receptors on dopaminergic neurons mediate nicotine reward and anxiety relief

    PubMed Central

    McGranahan, Tresa M.; Patzlaff, Natalie E.; Grady, Sharon R.; Heinemann, Stephen F.; Booker, T.K.

    2012-01-01

    Nicotine is the primary psychoactive substance in tobacco and it exerts its effects by interaction with various subtypes of nicotinic acetylcholine receptors (nAChRs) in the brain. One of the major subtypes expressed in brain, the alpha4beta2-nAChR, endogenously modulates neuronal excitability and thereby, modifies certain normal, as well as nicotine-induced, behaviors. Although alpha4-containing nAChRs are widely expressed across the brain, a major focus has been on their roles within midbrain dopaminergic regions involved in drug addition, mental illness and movement control in humans. We developed a unique model system to examine the role of alpha4-nAChRs within dopaminergic neurons by a targeted genetic deletion of the alpha4 subunit from dopaminergic neurons in mice. The loss alpha4 mRNA and alpha4beta2-nAChRs from dopaminergic neurons was confirmed, as well as selective loss of alpha4beta2-nAChR function from dopaminergic but not GABAergic neurons. Two behaviors central to nicotine dependence, reward and anxiety relief, were examined. Alpha4-nAChRs specifically on dopaminergic neurons were demonstrated to be necessary for nicotine reward as measured by nicotine place preference, but not for another drug of addiction, cocaine. Alpha4-nAChRs are necessary for the anxiolytic effects of nicotine in the elevated plus maze and elimination of alpha4-beta2-nAChRs specifically from dopaminergic neurons decreased sensitivity to the anxiolytic effects of nicotine. Deletion of alpha4-nAChRs specifically from dopaminergic neurons also increased sensitivity to nicotine-induced locomotor depression, however nicotine-induced hypothermia was unaffected. This is the first work to develop a dopaminergic specific deletion of a nAChR subunit and examine resulting changes in nicotine behaviors. PMID:21795541

  19. Prenatal nicotine exposure increases apnoea and reduces nicotinic potentiation of hypoglossal inspiratory output in mice

    PubMed Central

    Robinson, Dean M; Peebles, Karen C; Kwok, Henry; Adams, Brandon M; Clarke, Lan-Ling; Woollard, Gerald A; Funk, Gregory D

    2002-01-01

    We examined the effects of in utero nicotine exposure on postnatal development of breathing pattern and ventilatory responses to hypoxia (7.4 % O2) using whole-body plethysmography in mice at postnatal day 0 (P0), P3, P9, P19 and P42. Nicotine delayed early postnatal changes in breathing pattern. During normoxia, control and nicotine-exposed P0 mice exhibited a high frequency of apnoea (fA) which declined by P3 in control animals (from 6.7 ± 0.7 to 2.2 ± 0.7 min−1) but persisted in P3 nicotine-exposed animals (5.4 ± 1.3 min−1). Hypoxia induced a rapid and sustained reduction in fA except in P0 nicotine-exposed animals where it fell initially and then increased throughout the hypoxic period. During recovery, fA increased above control levels in both groups at P0. By P3 this increase was reduced in control but persisted in nicotine-exposed animals. To examine the origin of differences in respiratory behaviour, we compared the activity of hypoglossal (XII) nerves and motoneurons in medullary slice preparations. The frequency and variability of the respiratory rhythm and the envelope of inspiratory activity in XII nerves and motoneurons were indistinguishable between control and nicotine-exposed animals. Activation of postsynaptic nicotine receptors caused an inward current in XII motoneurons that potentiated XII nerve burst amplitude by 25 ± 5 % in control but only 14 ± 3 % in nicotine-exposed animals. Increased apnoea following nicotine exposure does not appear to reflect changes in basal activity of rhythm or pattern-generating networks, but may result, in part, from reduced nicotinic modulation of XII motoneurons. PMID:11826179

  20. Hydrogen occupancy in the RNi{sub 4}Mg (R=Y, La, Ce, and Nd) intermetallic compounds and hydrides

    SciTech Connect

    Hahn-Herrera, Otto; Orgaz, Emilio; Aburto, Andrea

    2009-10-15

    We have investigated the effect of hydrogen on the electronic strtucture of the RNi{sub 4}Mg (R=Y, La, Ce, Pr, and Nd) intermetallics. By means of a two-step approach, the projected plane-wave and linearized plane-waves methods, we studied the hydrogen-insertion energetics on the intermetallic matrix and the H-vacancy formation in the hydride compound. We found that particular interstitial sites in the intermetallics are suitable to allocate hydrogen and form a solid solution. The effect of these interstitials on the electronic structure is discussed. In the other hand, the hydrogen-occupied sites in the hydride are found to be energetically equivalent.

  1. Need for validation of Fagerstrom Test for Nicotine Dependence in Indian Context: Implications for Nicotine Replacement Therapy

    PubMed Central

    Sharma, Manoj Kumar; Sharma, Priyamvada

    2016-01-01

    Background: Variety of smokeable and chewable tobacco products with diverse nicotine content are used in India. Nicotine quantity in tobacco products has a direct bearing on developing tobacco dependence. The present work used this information to derive scores on the Fagerstrom test for nicotine dependence (FTND). It was used to determine the dosing of nicotine replacement treatment (NRT). Materials and Methods: Nicotine score quantitation was taken from the previous study. This data was applied to FTND to determine the relationship of nicotine content to the potential degree of dependence. Results: Application of nicotine quantitation to FTND in a hypothetical experiment significantly altered the scores from medium to high depending on the brand the used. Conclusion: Application of qunatitation of nicotine content in FTND score has implications for the assessment of tobacco dependence and NRT dose. The study implies validation of FTND using nicotine quantity in the consumed tobacco product as a scorable parameter in the FTND. PMID:27114620

  2. Nicotine chemistry, metabolism, kinetics and biomarkers.

    PubMed

    Benowitz, Neal L; Hukkanen, Janne; Jacob, Peyton

    2009-01-01

    Nicotine underlies tobacco addiction, influences tobacco use patterns, and is used as a pharmacological aid to smoking cessation. The absorption, distribution and disposition characteristics of nicotine from tobacco and medicinal products are reviewed. Nicotine is metabolized primarily by the liver enzymes CYP2A6, UDPglucuronosyltransferase (UGT), and flavin-containing monooxygenase (FMO). In addition to genetic factors, nicotine metabolism is influenced by diet and meals, age, sex, use of estrogen-containing hormone preparations, pregnancy and kidney disease, other medications, and smoking itself. Substantial racial/ethnic differences are observed in nicotine metabolism, which are likely influenced by both genetic and environmental factors. The most widely used biomarker of nicotine intake is cotinine, which may be measured in blood, urine, saliva, hair, or nails. The current optimal plasma cotinine cut-point to distinguish smokers from non-smokers in the general US population is 3 ng ml(-1). This cut-point is much lower than that established 20 years ago, reflecting less secondhand smoke exposure due to clear air policies and more light or occasional smoking. PMID:19184645

  3. Nicotine Chemistry, Metabolism, Kinetics and Biomarkers

    PubMed Central

    Hukkanen, Janne; Jacob, Peyton

    2010-01-01

    Nicotine underlies tobacco addiction, influences tobacco use patterns, and is used as a pharmacological aid to smoking cessation. The absorption, distribution and disposition characteristics of nicotine from tobacco and medicinal products are reviewed. Nicotine is metabolized primarily by the liver enzymes CYP2A6, UDP-glucuronosyltransfease (UGT), and flavin-containing monooxygenase (FMO). In addition to genetic factors, nicotine metabolism is influenced by diet and meals, age, sex, use of estrogen-containing hormone preparations, pregnancy and kidney disease, other medications, and smoking itself. Substantial racial/ethnic differences are observed in nicotine metabolism, which are likely influenced by both genetic and environmental factors. The most widely used biomarker of nicotine intake is cotinine, which may be measured in blood, urine, saliva, hair, or nails. The current optimal plasma cotinine cut-point to distinguish smokers from non-smokers in the general US population is 3 ng ml−1. This cut-point is much lower than that established 20 years ago, reflecting less secondhand smoke exposure due to clear air policies and more light or occasional smoking. PMID:19184645

  4. Nicotinic alteration of functional thalamocortical topography.

    PubMed

    Lee, Charles C; Yanagawa, Yuchio; Imaizumi, Kazuo

    2015-08-19

    The thalamocortical pathways form highly topographic connections from the primary sensory thalamic nuclei to the primary cortical areas. The synaptic properties of these thalamocortical connections are modifiable by activation from various neuromodulators, such as acetylcholine. Cholinergic activation can alter functional properties in both the developing and the mature nervous system. Moreover, environmental factors, such as nicotine, can activate these receptors, although the circuit-level alterations resulting from such nicotinic activation of sensory neural circuits remain largely unexplored. Therefore, we examined alterations to the functional topography of thalamocortical circuits in the developing sensory pathways of the mouse. Photostimulation by uncaging of glutamate was used to map these functional thalamocortical alterations in response to nicotinic receptor activation. As a result, we found that activation of forebrain nicotinic acetylcholine receptors results in an expansion and enhancement of functional thalamocortical topographies as assessed in brain slice preparations using laser-scanning photostimulation by uncaging of glutamate. These physiological changes were correlated with the neuroanatomical expression of nicotinic acetylcholine receptor subtypes (α7 and β2). These circuit-level alterations may provide a neural substrate underlying the plastic development and reshaping of thalamocortical circuitry in response to nicotinic receptor activation. PMID:26164456

  5. The α3β4* nicotinic acetylcholine receptor subtype mediates nicotine reward and physical nicotine withdrawal signs independently of the α5 subunit in the mouse

    PubMed Central

    Jackson, Kia J.; Sanjakdar, Sarah S.; Muldoon, Pretal P.; McIntosh, J. Michael; Damaj, M. Imad

    2013-01-01

    The 15q25 gene cluster contains genes that code for the α5, α3, and β4 nicotinic acetylcholine receptor (nAChRs) subunits, and in human genetic studies, has shown the most robust association with smoking behavior and nicotine dependence to date. The limited available animal studies implicate a role for the α5 and β4 nAChR subunits in nicotine dependence and withdrawal; however studies focusing on the behavioral role of the α3β4* nAChR receptor subtype in nicotine dependence are lacking. Because of the apparent role of the α3β4* nAChR subtype in nicotine dependence, the goal of the current study was to better evaluate the involvement of this subtype in nicotine mediated behavioral responses. Using the selective α3β4* nAChR antagonist, α-conotoxin AuIB, we assessed the role of α3β4* nAChRs in acute nicotine, nicotine reward, and physical and affective nicotine withdrawal. Because α5 has also been implicated in nicotine dependence behaviors in mice and can form functional receptors with α3β4*, we also evaluated the role of the α3β4α5* nAChR subtype in nicotine reward and somatic nicotine withdrawal signs by blocking the α3β4* nAChR subtype in α5 nAChR knockout mice with AuIB. AuIB had no significant effect on acute nicotine behaviors, but dose-dependently attenuated nicotine reward and physical withdrawal signs, with no significant effect in affective withdrawal measures. Interestingly, AuIB also attenuated nicotine reward and somatic signs in α5 nAChR knockout mice. This study shows that α3β4* nAChRs mediate nicotine reward and physical nicotine withdrawal, but not acute nicotine behaviors or affective nicotine withdrawal signs in mice. The α5 subunit is not required in the receptor assembly to mediate these effects. Our findings suggest an important role for the α3β4* nAChR subtype in nicotine reward and physical aspects of the nicotine withdrawal syndrome. PMID:23416040

  6. Nicotine evokes kinetic tremor by activating the inferior olive via α7 nicotinic acetylcholine receptors.

    PubMed

    Kunisawa, Naofumi; Iha, Higor A; Shimizu, Saki; Tokudome, Kentaro; Mukai, Takahiro; Kinboshi, Masato; Serikawa, Tadao; Ohno, Yukihiro

    2016-11-01

    Nicotinic acetylcholine (nACh) receptors are implicated in the pathogenesis of movement disorders (e.g., tremor) and epilepsy. Here, we performed behavioral and immunohistochemical studies using mice and rats to elucidate the mechanisms underlying nicotine-induced tremor. Treatments of animals with nicotine (0.5-2mg/kg, i.p.) elicited kinetic tremor, which was completely suppressed by the nACh receptor antagonist mecamylamine (MEC). The specific α7 nACh receptor antagonist methyllycaconitine (MLA) also inhibited nicotine-induced tremor, whereas the α4β2 nACh antagonist dihydro-β-erythroidine (DHβE) or the peripheral α3β4 nACh antagonist hexamethonium showed no effects. Mapping analysis of Fos protein expression, a biological marker of neural excitation, revealed that a tremorgenic dose (1mg/kg) of nicotine region-specifically elevated Fos expression in the piriform cortex (PirC), medial habenula, solitary nucleus and inferior olive (IO) among 44 brain regions examined. In addition, similarly to the tremor responses, nicotine-induced Fos expression in the PirC and IO was selectively antagonized by MLA, but not by DHβE. Furthermore, an electrical lesioning of the IO, but not the PirC, significantly suppressed the induction of nicotine tremor. The present results suggest that nicotine elicits kinetic tremor in rodents by activating the IO neurons via α7 nACh receptors. PMID:27506652

  7. Effects of prenatal nicotine on expression of nicotine receptor subunits in the fetal brain

    PubMed Central

    Lv, Juanxiu; Mao, Caiping; Zhu, Liyan; Zhang, Hong; Pengpeng, Hui; Xu, Feichao; Liu, Yujuan; Zhang, Lubo; Xu, Zhice

    2008-01-01

    Previous studies have suggested that prenatal exposure to nicotine is associated with abnormal development in fetuses, including fetal brain damage. The present study determined the effect of maternal administration of nicotine during different gestational periods on brain nicotine receptor subunits in fetal rats. Subcutaneous injections of nicotine in maternal rats from the early and middle gestation decreased fetal blood PO2, increased fetal blood PCO2 and hemoglobin, and decreased fetal brain weight. The nicotinic acetylcholine receptor (nAChRs) mRNA abundance in the fetal brain was significantly changed by prenatal treatment with nicotine during pregnancy. Fetal α2, α4, α7, and β2 units were significantly increased in the brain by prenatal exposure to nicotine in rat fetuses. However, the expression of mRNA of fetal brain α3, α5, β3, and β4 units were not changed. The results showed that prenatal nicotine can change the development of both α and β subunits of nAChRs in the fetal brain at gene level in association with restriction of fetal brain growth and in utero hypoxia. PMID:18541304

  8. NICOTINE EFFECTS ON THE ACTIVITY OF MICE EXPOSED PRENATALLY TO THE NICOTINIC AGONIST ANATOXIN-A.

    EPA Science Inventory

    Considerable research has shown long-lasting effects of early exposure in experimental animals to nicotine. Anatoxin-a is produced by cyanobacteria and has been shown to be a potent nicotinic agonist. This experiment evaluated the motor activity of adult mice, and their respons...

  9. Effects of chronic varenicline treatment on nicotine, cocaine, and concurrent nicotine+cocaine self-administration.

    PubMed

    Mello, Nancy K; Fivel, Peter A; Kohut, Stephen J; Carroll, F Ivy

    2014-04-01

    Nicotine dependence and cocaine abuse are major public health problems, and most cocaine abusers also smoke cigarettes. An ideal treatment medication would reduce both cigarette smoking and cocaine abuse. Varenicline is a clinically available, partial agonist at α4β2* and α6β2* nicotinic acetylcholine receptors (nAChRs) and a full agonist at α7 nAChRs. Varenicline facilitates smoking cessation in clinical studies and reduced nicotine self-administration, and substituted for the nicotine-discriminative stimulus in preclinical studies. The present study examined the effects of chronic varenicline treatment on self-administration of IV nicotine, IV cocaine, IV nicotine+cocaine combinations, and concurrent food-maintained responding by five cocaine- and nicotine-experienced adult rhesus monkeys (Macaca mulatta). Varenicline (0.004-0.04 mg/kg/h) was administered intravenously every 20 min for 23 h each day for 7-10 consecutive days. Each varenicline treatment was followed by saline-control treatment until food- and drug-maintained responding returned to baseline. During control treatment, nicotine+cocaine combinations maintained significantly higher levels of drug self-administration than nicotine or cocaine alone (P<0.05-0.001). Varenicline dose-dependently reduced responding maintained by nicotine alone (0.0032 mg/kg/inj) (P<0.05), and in combination with cocaine (0.0032 mg/kg/inj) (P<0.05) with no significant effects on food-maintained responding. However, varenicline did not significantly decrease self-administration of a low dose of nicotine (0.001 mg/kg), cocaine alone (0.0032 and 0.01 mg/kg/inj), or 0.01 mg/kg cocaine combined with the same doses of nicotine. We conclude that varenicline selectively attenuates the reinforcing effects of nicotine alone but not cocaine alone, and its effects on nicotine+cocaine combinations are dependent on the dose of cocaine. PMID:24304823

  10. Nicotine induces fibrogenic changes in human liver via nicotinic acetylcholine receptors expressed on hepatic stellate cells

    SciTech Connect

    Soeda, Junpei; Morgan, Maelle; McKee, Chad; Mouralidarane, Angelina; Lin, ChingI; Roskams, Tania; Oben, Jude A.

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Cigarette smoke may induce liver fibrosis via nicotine receptors. Black-Right-Pointing-Pointer Nicotine induces proliferation of hepatic stellate cells (HSCs). Black-Right-Pointing-Pointer Nicotine activates hepatic fibrogenic pathways. Black-Right-Pointing-Pointer Nicotine receptor antagonists attenuate HSC proliferation. Black-Right-Pointing-Pointer Nicotinic receptor antagonists may have utility as novel anti-fibrotic agents. -- Abstract: Background and aims: Cigarette smoke (CS) may cause liver fibrosis but possible involved mechanisms are unclear. Among the many chemicals in CS is nicotine - which affects cells through nicotinic acetylcholine receptors (nAChR). We studied the effects of nicotine, and involved pathways, on human primary hepatic stellate cells (hHSCs), the principal fibrogenic cells in the liver. We then determined possible disease relevance by assaying nAChR in liver samples from human non-alcoholic steatohepatitis (NASH). Methods: hHSC were isolated from healthy human livers and nAChR expression analyzed - RT-PCR and Western blotting. Nicotine induction of hHSC proliferation, upregulation of collagen1-{alpha}2 and the pro-fibrogenic cytokine transforming growth factor beta 1 (TGF-{beta}1) was determined along with involved intracellular signaling pathways. nAChR mRNA expression was finally analyzed in whole liver biopsies obtained from patients diagnosed with non-alcoholic steatohepatitis (NASH). Results: hHSCs express muscle type ({alpha}1, {beta}1, delta and epsilon) and neuronal type ({alpha}3, {alpha}6, {alpha}7, {beta}2 and {beta}4) nAChR subunits at the mRNA level. Among these subunits, {alpha}3, {alpha}7, {beta}1 and {epsilon} were predominantly expressed as confirmed by Western blotting. Nicotine induced hHSC proliferation was attenuated by mecamylamine (p < 0.05). Additionally, collagen1-{alpha}2 and TGF-{beta}1 mRNA expression were significantly upregulated by nicotine and inhibited by

  11. Nicotine Administration Attenuates Methamphetamine-Induced Novel Object Recognition Deficits

    PubMed Central

    Vieira-Brock, Paula L.; McFadden, Lisa M.; Nielsen, Shannon M.; Smith, Misty D.; Hanson, Glen R.

    2015-01-01

    Background: Previous studies have demonstrated that methamphetamine abuse leads to memory deficits and these are associated with relapse. Furthermore, extensive evidence indicates that nicotine prevents and/or improves memory deficits in different models of cognitive dysfunction and these nicotinic effects might be mediated by hippocampal or cortical nicotinic acetylcholine receptors. The present study investigated whether nicotine attenuates methamphetamine-induced novel object recognition deficits in rats and explored potential underlying mechanisms. Methods: Adolescent or adult male Sprague-Dawley rats received either nicotine water (10–75 μg/mL) or tap water for several weeks. Methamphetamine (4×7.5mg/kg/injection) or saline was administered either before or after chronic nicotine exposure. Novel object recognition was evaluated 6 days after methamphetamine or saline. Serotonin transporter function and density and α4β2 nicotinic acetylcholine receptor density were assessed on the following day. Results: Chronic nicotine intake via drinking water beginning during either adolescence or adulthood attenuated the novel object recognition deficits caused by a high-dose methamphetamine administration. Similarly, nicotine attenuated methamphetamine-induced deficits in novel object recognition when administered after methamphetamine treatment. However, nicotine did not attenuate the serotonergic deficits caused by methamphetamine in adults. Conversely, nicotine attenuated methamphetamine-induced deficits in α4β2 nicotinic acetylcholine receptor density in the hippocampal CA1 region. Furthermore, nicotine increased α4β2 nicotinic acetylcholine receptor density in the hippocampal CA3, dentate gyrus and perirhinal cortex in both saline- and methamphetamine-treated rats. Conclusions: Overall, these findings suggest that nicotine-induced increases in α4β2 nicotinic acetylcholine receptors in the hippocampus and perirhinal cortex might be one mechanism by which

  12. Decreased nicotinic receptor availability in smokers with slow rates of nicotine metabolism

    PubMed Central

    Dubroff, Jacob G.; Doot, Robert K.; Falcone, Mary; R, Robert A. Schnoll; Ray, Riju; Tyndale, Rachel F.; Brody, Arthur L.; Hou, Catherine; Schmitz, Alexander; Lerman, Caryn

    2015-01-01

    The nicotine metabolite ratio (NMR), a stable measure of hepatic nicotine metabolism via the CYP2A6 pathway and total nicotine clearance, is a predictive biomarker of response to nicotine replacement therapy, with increased quit rates in slower metabolizers. Nicotine binds directly to nicotinic acetylcholine receptors (nAChRs) to exert its psychoactive effects. This study examined the relationship between NMR and nAChR availability (α4β2* subtype) using positron emission tomography (PET) imaging of the radiotracer 2-18F-FA-85380 (2-18F-FA). Methods Twenty four smokers, 12 slow metabolizers (NMR <0.26) and 12 normal metabolizers (NMR ≥0.26), underwent 2-18F-FA-PET brain imaging following overnight nicotine abstinence (18 hours prior to scanning), using a validated bolus plus infusion protocol. Availability of nAChRs was compared between NMR groups in a priori volumes of interest (VOIs), with total distribution volume (VT/fP) being the measure of nAChR availability. Cravings to smoke were assessed prior to and following the scans. Results Thalamic nAChR α4β2* availability was significantly reduced in slow (versus normal) nicotine metabolizers (P=0.04). Slow metabolizers exhibited greater reductions in craving than normal metabolizers from pre- to post-scanning; however, craving was unrelated to availability. Conclusion The rate of nicotine metabolism is associated with thalamic nAChR availability. Additional studies could examine whether altered nAChR availability underlies differences in treatment response between slow and normal metabolizers of nicotine. PMID:26272810

  13. Habenula cholinergic neurons regulate anxiety during nicotine withdrawal via nicotinic acetylcholine receptors.

    PubMed

    Pang, Xueyan; Liu, Liwang; Ngolab, Jennifer; Zhao-Shea, Rubing; McIntosh, J Michael; Gardner, Paul D; Tapper, Andrew R

    2016-08-01

    Cholinergic neurons in the medial habenula (MHb) modulate anxiety during nicotine withdrawal although the molecular neuroadaptation(s) within the MHb that induce affective behaviors during nicotine cessation is largely unknown. MHb cholinergic neurons are unique in that they robustly express neuronal nicotinic acetylcholine receptors (nAChRs), although their behavioral role as autoreceptors in these neurons has not been described. To test the hypothesis that nAChR signaling in MHb cholinergic neurons could modulate anxiety, we expressed novel "gain of function" nAChR subunits selectively in MHb cholinergic neurons of adult mice. Mice expressing these mutant nAChRs exhibited increased anxiety-like behavior that was alleviated by blockade with a nAChR antagonist. To test the hypothesis that anxiety induced by nicotine withdrawal may be mediated by increased MHb nicotinic receptor signaling, we infused nAChR subtype selective antagonists into the MHb of nicotine naïve and withdrawn mice. While antagonists had little effect on nicotine naïve mice, blocking α4β2 or α6β2, but not α3β4 nAChRs in the MHb alleviated anxiety in mice undergoing nicotine withdrawal. Consistent with behavioral results, there was increased functional expression of nAChRs containing the α6 subunit in MHb neurons that also expressed the α4 subunit. Together, these data indicate that MHb cholinergic neurons regulate nicotine withdrawal-induced anxiety via increased signaling through nicotinic receptors containing the α6 subunit and point toward nAChRs in MHb cholinergic neurons as molecular targets for smoking cessation therapeutics. PMID:27020042

  14. Transcriptional regulation by nicotine in dopaminergic neurons

    PubMed Central

    Henley, Beverley M.; Williams, Brian A.; Srinivasan, Rahul; Cohen, Bruce N.; Xiao, Cheng; Mackey, Elisha D.W.; Wold, Barbara J.; Lester, Henry A.

    2013-01-01

    Dopaminergic neurons in the substantia nigra pars compacta (SNc) degenerate in Parkinson’s disease. These neurons robustly express several nicotinic acetylcholine receptor (nAChR) subtypes. Smoking appears to be neuroprotective for Parkinson’s disease but the mechanism is unknown. To determine whether chronic nicotine-induced changes in gene expression contribute to the neuroprotective effects of smoking, we develop methods to measure the effect of prolonged nicotine exposure on the SNc neuronal transcriptome in an unbiased manner. Twenty neurons were collected using laser-capture microscopy and transcriptional changes were assessed using RNA deep sequencing. These results are the first whole-transcriptome analyses of chronic nicotine treatment in SNc neurons. Overall, 129 genes were significantly regulated: 67 upregulated, 62 downregulated. Nicotine-induced relief of endoplasmic reticulum (ER) stress has been postulated as a potential mechanism for the neuroprotective effects of smoking. Chronic nicotine did not significantly affect the expression of ER stress-related genes, nor of dopamine-related or nAChR genes, but it did modulate expression of 129 genes that could be relevant to the neuroprotective effects of smoking, including genes involved in (1) the ubiquitin–proteasome pathway, (2) cell cycle regulation, (3) chromatin modification, and (4) DNA binding and RNA regulation. We also report preliminary transcriptome data for single-cell dopaminergic and GABAergic neurons isolated from midbrain cultures. These novel techniques will facilitate advances in understanding the mechanisms taking place at the cellular level and may have applications elsewhere in the fields of neuroscience and molecular biology. The results give an emerging picture of the role of nicotine on the SNc and on dopaminergic neurons. PMID:23939186

  15. Nicotine recruits glutamate receptors to postsynaptic sites.

    PubMed

    Duan, Jing-Jing; Lozada, Adrian F; Gou, Chen-Yu; Xu, Jing; Chen, Yuan; Berg, Darwin K

    2015-09-01

    Cholinergic neurons project throughout the nervous system and activate nicotinic receptors to modulate synaptic function in ways that shape higher order brain function. The acute effects of nicotinic signaling on long-term synaptic plasticity have been well-characterized. Less well understood is how chronic exposure to low levels of nicotine, such as those encountered by habitual smokers, can alter neural connections to promote addiction and other lasting behavioral effects. We show here that chronic exposure of hippocampal neurons in culture to low levels of nicotine recruits AMPA and NMDA receptors to the cell surface and sequesters them at postsynaptic sites. The receptors include GluA2-containing AMPA receptors, which are responsible for most of the excitatory postsynaptic current mediated by AMPA receptors on the neurons, and include NMDA receptors containing GluN1 and GluN2B subunits. Moreover, we find that the nicotine treatment also increases expression of the presynaptic component synapsin 1 and arranges it in puncta juxtaposed to the additional AMPA and NMDA receptor puncta, suggestive of increases in synaptic contacts. Consistent with increased synaptic input, we find that the nicotine treatment leads to an increase in the excitatory postsynaptic currents mediated by AMPA and NMDA receptors. Further, the increases skew the ratio of excitatory-to-inhibitory input that the cell receives, and this holds both for pyramidal neurons and inhibitory neurons in the hippocampal CA1 region. The GluN2B-containing NMDA receptor redistribution at synapses is associated with a significant increase in GluN2B phosphorylation at Tyr1472, a site known to prevent GluN2B endocytosis. These results suggest that chronic exposure to low levels of nicotine not only alters functional connections but also is likely to change excitability levels across networks. Further, it may increase the propensity for synaptic plasticity, given the increase in synaptic NMDA receptors. PMID

  16. Microstructure and dielectric tunable properties of Ba0.6Sr0.4TiO3-Mg2SiO4-MgO composite.

    PubMed

    He, Yanyan; Xu, Yebin; Liu, Ting; Zeng, Chunlian; Chen, Wanping

    2010-07-01

    Ba(0.6)Sr(0.4)TiO(3)-Mg(2)SiO(4)-MgO composite ceramics were prepared by a solid-state reaction method and their dielectric tunable characteristics were investigated for the potential application as microwave tunable materials. The addition of Mg(2)SiO(4)-MgO into Ba(0.6)Sr(0.4)TiO(3) forms ferroelectric (Ba(0.6)Sr(0.4)TiO(3))-dielectric (Mg(2)SiO(4)-MgO) composites and shifts the Curie temperature to a lower temperature. The dielectric constant and loss tangent of Ba(0.6)Sr(0.4)TiO(3)-Mg(2)Si(O4)- MgO composites have been decreased and the overall tunability is maintained at a sufficiently high level. The microwave dielectric properties of Ba(0.6)Sr(0.4)TiO(3)-Mg(2)Si(O4)-MgO composites were evaluated. Ba(0.6)Sr(0.4)TiO(3)-Mg(2)SiO(4)-MgO composites have tunability of 9.2 to 10.5% at 100 kHz under 2 kV/mm, indicating that it is a promising candidate material for tunable microwave applications requiring a low dielectric constant. PMID:20639146

  17. E-Cig Liquid Nicotine Containers Often Mislabeled

    MedlinePlus

    ... medlineplus.gov/news/fullstory_160108.html E-Cig Liquid Nicotine Containers Often Mislabeled Also, many aren't ... July 27, 2016 (HealthDay News) -- Containers that hold liquid nicotine for electronic cigarettes may not be labeled ...

  18. Intracerebellar behavioral interactions between nicotine, cotinine and ethanol in mice

    SciTech Connect

    Dar, M.S.; Li, C. )

    1992-02-26

    Using ethanol-induced motor incoordination as the test response as evaluated by rotorod, possible behavioral interactions between ethanol and (-)-nicotine in the cerebellum, one of the key motor area, were investigated. (-)-Nicotine, 5, 1.25, 0.625 ng/100nL intracerebellarly significantly attenuated motor incoordination due to ethanol in a dose-dependent manner. Similarly, (-)-cotinine, a major metabolite of nicotine, 5, 2.5, and 1.25 ng/100nL, significantly but less marked compared to (-)-nicotine attenuated ethanol-induced motor incoordination. The highest, 5 ng/100nL, dose of (-)-nicotine or (-)-cotinine followed by saline instead of ethanol did not alter normal motor coordination. The attenuation of ethanol-induced motor incoordination by (-)-nicotine and (-)- cotinine was blocked by intracerebellar hexamethonium 1 ug/100nL, a purported nicotinic cholinergic antagonist. The data obtained strongly suggest participation of cerebellar nicotinic cholinergic receptor in the ethanol-induced motor incoordination.

  19. Disentangling the nature of the nicotine stimulus✩

    PubMed Central

    Bevins, Rick A.; Barrett, Scott T.; Polewan, Robert J.; Pittenger, Steven T.; Swalve, Natashia; Charntikov, Sergios

    2011-01-01

    Learning involving interoceptive stimuli likely plays an important role in many diseases and psychopathologies. Within this area, there has been extensive research investigating the interoceptive stimulus effects of abused drugs. In this pursuit, behavioral pharmacologists have taken advantage of what is known about learning processes and adapted the techniques to investigate the behavioral and receptor mechanisms of drug stimuli. Of particular interest is the nicotine stimulus and the use of the two-lever operant drug discrimination task and the Pavlovian drug discriminated goal-tracking task. There is strong concordance between the two methods when using “standard” testing protocols that minimize learning on test days. For example, ABT-418, nornicotine, and varenicline all fully evoked nicotine-appropriate responding. Notably, research from our laboratory with the discriminated goal-tracking task has used an alternative testing protocol. This protocol assesses stimulus substitution based on how well extinction learning using a non-nicotine ligand transfers back to the nicotine stimulus. These findings challenge conclusions based on more “standard” testing procedures (e.g., ABT-418 is not nicotine-like). As a starting point, we propose Thurstone scaling as a quantitative method for more precisely comparing transfer of extinction across doses, experiments, and investigators. We close with a discussion of future research directions and potential implications of the research for understanding interoceptive stimuli. PMID:22119845

  20. Central administration of nicotine suppresses tracheobronchial cough in anesthetized cats

    PubMed Central

    Rose, M. J.; Pitts, T. E.; Mortensen, A.; Corrie, L. W.; Davenport, P. W.; Bolser, D. C.

    2014-01-01

    We tested the hypothesis that nicotine, which acts peripherally to promote coughing, might inhibit reflex cough at a central site. Nicotine was administered via the vertebral artery [intra-arterial (ia)] to the brain stem circulation and by microinjections into a restricted area of the caudal ventral respiratory column in 33 pentobarbital anesthetized, spontaneously breathing cats. The number of coughs induced by mechanical stimulation of the tracheobronchial airways; amplitudes of the diaphragm, abdominal muscle, and laryngeal muscles EMGs; and several temporal characteristics of cough were analyzed after administration of nicotine and compared with those during control and recovery period. (−)Nicotine (ia) reduced cough number, cough expiratory efforts, blood pressure, and heart rate in a dose-dependent manner. (−)Nicotine did not alter temporal characteristics of the cough motor pattern. Pretreatment with mecamylamine prevented the effect of (−)nicotine on blood pressure and heart rate, but did not block the antitussive action of this drug. (+)Nicotine was less potent than (−)nicotine for inhibition of cough. Microinjections of (−)nicotine into the caudal ventral respiratory column produced similar inhibitory effects on cough as administration of this isomer by the ia route. Mecamylamine microinjected in the region just before nicotine did not significantly reduce the cough suppressant effect of nicotine. Nicotinic acetylcholine receptors significantly modulate functions of brain stem and in particular caudal ventral respiratory column neurons involved in expression of the tracheobronchial cough reflex by a mecamylamine-insensitive mechanism. PMID:25477349

  1. Central administration of nicotine suppresses tracheobronchial cough in anesthetized cats.

    PubMed

    Poliacek, I; Rose, M J; Pitts, T E; Mortensen, A; Corrie, L W; Davenport, P W; Bolser, D C

    2015-02-01

    We tested the hypothesis that nicotine, which acts peripherally to promote coughing, might inhibit reflex cough at a central site. Nicotine was administered via the vertebral artery [intra-arterial (ia)] to the brain stem circulation and by microinjections into a restricted area of the caudal ventral respiratory column in 33 pentobarbital anesthetized, spontaneously breathing cats. The number of coughs induced by mechanical stimulation of the tracheobronchial airways; amplitudes of the diaphragm, abdominal muscle, and laryngeal muscles EMGs; and several temporal characteristics of cough were analyzed after administration of nicotine and compared with those during control and recovery period. (-)Nicotine (ia) reduced cough number, cough expiratory efforts, blood pressure, and heart rate in a dose-dependent manner. (-)Nicotine did not alter temporal characteristics of the cough motor pattern. Pretreatment with mecamylamine prevented the effect of (-)nicotine on blood pressure and heart rate, but did not block the antitussive action of this drug. (+)Nicotine was less potent than (-)nicotine for inhibition of cough. Microinjections of (-)nicotine into the caudal ventral respiratory column produced similar inhibitory effects on cough as administration of this isomer by the ia route. Mecamylamine microinjected in the region just before nicotine did not significantly reduce the cough suppressant effect of nicotine. Nicotinic acetylcholine receptors significantly modulate functions of brain stem and in particular caudal ventral respiratory column neurons involved in expression of the tracheobronchial cough reflex by a mecamylamine-insensitive mechanism. PMID:25477349

  2. Concurrent access to nicotine and sucrose in rats

    PubMed Central

    Hogarth, Lee; Shoaib, Mohammed

    2014-01-01

    Background Animal models that allow concurrent access to drug and nondrug reinforcers provide unique insight into the etiology, maintenance, and treatment of drug use. Objectives We sought to develop and utilize a concurrent access procedure with nicotine and sucrose in rats. Methods Pressing one lever delivered intravenous nicotine, and pressing another lever delivered sucrose pellets, with both reinforcers freely available throughout daily sessions. Results Rats that had been pretrained with nicotine on some days and sucrose on other days responded on both levers when subsequently given concurrent access, but almost all responded at substantially higher rates on the sucrose lever. In contrast, rats pretrained exclusively with nicotine before being given concurrent access showed individual differences, with about half responding more on the nicotine lever. Treatment with the nicotinic receptor partial agonist varenicline selectively decreased nicotine self-administration. Food restriction and removal of the sucrose lever both increased nicotine self-administration. Conclusions The finding that rats continue to take nicotine when sucrose is concurrently available—and in many cases take it more frequently than sucrose—demonstrates that nicotine self-administration does not only occur in the absence of alternative reinforcement options. As a model of human nicotine use, concurrent access is more naturalistic and has higher face validity than procedures in which only one reinforcer is available or choosing one reinforcer precludes access to other reinforcers. As such, this procedure could be useful for evaluating therapeutic agents and improving our understanding of environmental conditions that promote or discourage nicotine use. PMID:25366874

  3. Genetic Factors for Enhancement of Nicotine Levels in Cultivated Tobacco

    PubMed Central

    Wang, Bingwu; Lewis, Ramsey S.; Shi, Junli; Song, Zhongbang; Gao, Yulong; Li, Wenzheng; Chen, Hongxia; Qu, Rongda

    2015-01-01

    Nicotine has practical applications relating to smoking cessation devices and alternative nicotine products. Genetic manipulation for increasing nicotine content in cultivated tobacco (Nicotiana tabacum L.) may be of value for industrial purposes, including the possibility of enhancing the efficiency of nicotine extraction. Biotechnological approaches have been evaluated in connection with this objective, but field-based results are few. Here, we report characterization of two genes encoding basic-helix-loop-helix (bHLH) transcription factors (TFs), NtMYC2a and NtMYC2b from tobacco. Overexpression of NtMYC2a increased leaf nicotine levels in T1 transgenic lines approximately 2.3-fold in greenhouse-grown plants of tobacco cultivar ‘NC 95′. Subsequent field testing of T2 and T3 generations of transgenic NtMYC2a overexpression lines showed nicotine concentrations were 76% and 58% higher than control lines, respectively. These results demonstrated that the increased nicotine trait was stably inherited to the T2 and T3 generations, indicating the important role that NtMYC2a plays in regulating nicotine accumulation in N. tabacum and the great potential of NtMYC2a overexpression in tobacco plants for industrial nicotine production. Collected data in this study also indicated a negative feedback inhibition of nicotine biosynthesis. Further enhancement of nicotine accumulation in tobacco leaf may require modification of the processes of nicotine transport and deposition. PMID:26626731

  4. Identification of the Escherichia coli Nicotinic Acid Mononucleotide Adenylyltransferase Gene

    PubMed Central

    Mehl, Ryan A.; Kinsland, Cynthia; Begley, Tadhg P.

    2000-01-01

    The gene (ybeN) coding for nicotinate mononucleotide adenylyltransferase, an NAD(P) biosynthetic enzyme, has been identified and overexpressed in Escherichia coli. This enzyme catalyzes the reversible adenylation of nicotinate mononucleotide and shows product inhibition. The rate of adenylation of nicotinate mononucleotide is at least 20 times faster than the rate of adenylation of nicotinamide mononucleotide. PMID:10894752

  5. Dopaminergic and cholinergic learning mechanisms in nicotine addiction.

    PubMed

    Subramaniyan, Manivannan; Dani, John A

    2015-09-01

    Nicotine addiction drives tobacco use by one billion people worldwide, causing nearly six million deaths a year. Nicotine binds to nicotinic acetylcholine receptors that are normally activated by the endogenous neurotransmitter acetylcholine. The widespread expression of nicotinic receptors throughout the nervous system accounts for the diverse physiological effects triggered by nicotine. A crucial influence of nicotine is on the synaptic mechanisms underlying learning that contribute to the addiction process. Here, we focus on the acquisition phase of smoking addiction and review animal model studies on how nicotine modifies dopaminergic and cholinergic signaling in key nodes of the reinforcement circuitry: ventral tegmental area, nucleus accumbens (NAc), amygdala, and hippocampus. Capitalizing on mechanisms that subserve natural rewards, nicotine activates midbrain dopamine neurons directly and indirectly, and nicotine causes dopamine release in very broad target areas throughout the brain, including the NAc, amygdala, and hippocampus. In addition, nicotine orchestrates local changes within those target structures, alters the release of virtually all major neurotransmitters, and primes the nervous system to the influence of other addictive drugs. Hence, understanding how nicotine affects the circuitry for synaptic plasticity and learning may aid in developing reasoned therapies to treat nicotine addiction. PMID:26301866

  6. Tobacco and Nicotine Product Testing

    PubMed Central

    Biener, Lois; Leischow, Scott J.; Zeller, Mitch R.

    2012-01-01

    Introduction: Tobacco product testing is a critical component of the Family Smoking Prevention and Tobacco Control Act (FSPTCA), which grants the Food and Drug Administration the authority to regulate tobacco products. The availability of methods and measures that can provide accurate data on the relative health risks across types of tobacco products, brands, and subbrands of tobacco products on the validity of any health claims associated with a product, and on how consumers perceive information on products toxicity or risks is crucial for making decisions on the product's potential impact on public health. These tools are also necessary for making assessments of the impact of new indications for medicinal products (other than cessation) but more importantly of tobacco products that may in the future be marketed as cessation tools. Objective: To identify research opportunities to develop empirically based and comprehensive methods and measures for testing tobacco and other nicotine-containing products so that the best science is available when decisions are made about products or policies. Methods: Literature was reviewed to address sections of the FSPTCA relevant to tobacco product evaluation; research questions were generated and then reviewed by a committee of research experts. Results: A research agenda was developed for tobacco product evaluation in the general areas of toxicity and health risks, abuse liability, consumer perception, and population effects. Conclusion: A cohesive, systematic, and comprehensive assessment of tobacco products is important and will require building consensus and addressing some crucial research questions. PMID:21460383

  7. Effects of nicotine, methamphetamine and cocaine on extracellular levels of acetylcholine in the interpeduncular nucleus of rats.

    PubMed

    Hussain, Rifat J; Taraschenko, Olga D; Glick, Stanley D

    2008-08-01

    There is increasing evidence that the cholinergic habenulo-interpeduncular pathway and the dopaminergic mesolimbic pathway may jointly mediate the reinforcing properties of addictive drugs. However, the effects of addictive drug on the functioning of the habenulo-interpeduncular pathway have not been well-characterized. Thus, several drugs of abuse (i.e., nicotine, cocaine, amphetamine) have been shown to alter the morphology of the habenulo-interpeduncular pathway, causing selective degeneration of the cholinergic neurons in this area. On the other hand, morphine was shown to alter the neurochemistry of the habenulo-interpeduncular pathway, inducing biphasic changes in acetylcholine release in the interpeduncular nucleus. In order to determine the effects of cocaine, amphetamine and nicotine on cholinergic neurotransmission in the habenulo-interpeduncular pathway, levels of acetylcholine were assessed during microdialysis in freely moving rats. Nicotine (0.1 and 0.4 mg/kg s.c.) produced a dose-dependent decrease in extracellular levels of acetylcholine, while methamphetamine (1 and 4 mg/kg i.p.) produced an increase in acetylcholine release in the interpeduncular nucleus. Cocaine (5 and 20 mg/kg i.p.) produced a biphasic effect on extracellular acetylcholine release, i.e., a low dose enhanced the release of acetylcholine and a high dose decreased its release. These results suggest that the habenulo-intepeduncular pathway may be a common target for drugs of abuse and, by modulating the mesolimbic pathway, may mediate unique aspects of the rewarding effects of different drugs. PMID:18583043

  8. Investigations of Enantiopure Nicotine Haptens Using an Adjuvanting Carrier in Anti-Nicotine Vaccine Development.

    PubMed

    Jacob, Nicholas T; Lockner, Jonathan W; Schlosburg, Joel E; Ellis, Beverly A; Eubanks, Lisa M; Janda, Kim D

    2016-03-24

    Despite efforts to produce suitable smoking cessation aids, addiction to nicotine continues to carry a substantive risk of recidivism. An attractive alternative to current therapies is the pharmacokinetic strategy of antinicotine vaccination. A major hurdle in the development of the strategy has been to elicit a sufficiently high antibody concentration to curb nicotine distribution to the brain. Herein, we detail investigations into a new hapten design, which was able to elicit an antibody response of significantly higher specificity for nicotine. We also explore the use of a mutant flagellin carrier protein with adjuvanting properties. These studies underlie the feasibility of improvement in antinicotine vaccine formulations to move toward clinical efficacy. PMID:26918428

  9. NICOTINE EFFECTS ON THE MOTOR ACTIVITY OF MICE EXPOSED PRENATALLY TO THE NICOTINIC AGONIST ANATOXIN-A.

    EPA Science Inventory

    Several studies in the literature have shown that exposure of mice and rats to nicotine early in development alters its effects when the rodents are subsequently challenged with nicotine. Anatoxin-a is a nicotinic agonist produced by several genera of cyanobacteria, and has caus...

  10. Adolescent nicotine induces persisting changes in development of neural connectivity.

    PubMed

    Smith, Robert F; McDonald, Craig G; Bergstrom, Hadley C; Ehlinger, Daniel G; Brielmaier, Jennifer M

    2015-08-01

    Adolescent nicotine induces persisting changes in development of neural connectivity. A large number of brain changes occur during adolescence as the CNS matures. These changes suggest that the adolescent brain may still be susceptible to developmental alterations by substances which impact its growth. Here we review recent studies on adolescent nicotine which show that the adolescent brain is differentially sensitive to nicotine-induced alterations in dendritic elaboration, in several brain areas associated with processing reinforcement and emotion, specifically including nucleus accumbens, medial prefrontal cortex, basolateral amygdala, bed nucleus of the stria terminalis, and dentate gyrus. Both sensitivity to nicotine, and specific areas responding to nicotine, differ between adolescent and adult rats, and dendritic changes in response to adolescent nicotine persist into adulthood. Areas sensitive to, and not sensitive to, structural remodeling induced by adolescent nicotine suggest that the remodeling generally corresponds to the extended amygdala. Evidence suggests that dendritic remodeling is accompanied by persisting changes in synaptic connectivity. Modeling, electrophysiological, neurochemical, and behavioral data are consistent with the implication of our anatomical studies showing that adolescent nicotine induces persisting changes in neural connectivity. Emerging data thus suggest that early adolescence is a period when nicotine consumption, presumably mediated by nicotine-elicited changes in patterns of synaptic activity, can sculpt late brain development, with consequent effects on synaptic interconnection patterns and behavior regulation. Adolescent nicotine may induce a more addiction-prone phenotype, and the structures altered by nicotine also subserve some emotional and cognitive functions, which may also be altered. We suggest that dendritic elaboration and associated changes are mediated by activity-dependent synaptogenesis, acting in part

  11. Binding, uptake, and release of nicotine by human gingival fibroblasts

    SciTech Connect

    Hanes, P.J.; Schuster, G.S.; Lubas, S. )

    1991-02-01

    Previous studies of the effects of nicotine on fibroblasts have reported an altered morphology and attachment of fibroblasts to substrates and disturbances in protein synthesis and secretion. This altered functional and attachment response may be associated with changes in the cell membrane resulting from binding of the nicotine, or to disturbances in cell metabolism as a result of high intracellular levels of nicotine. The purpose of the present study, therefore, was to (1) determine whether gingival fibroblasts bound nicotine and if any binding observed was specific or non-specific in nature; (2) determine whether gingival fibroblasts internalized nicotine, and if so, at what rate; (3) determine whether gingival fibroblasts also released nicotine back into the extracellular environment; and (4) if gingival fibroblasts release nicotine intact or as a metabolite. Cultures of gingival fibroblasts were prepared from gingival connective tissue biopsies. Binding was evaluated at 4{degree}C using a mixture of {sup 3}H-nicotine and unlabeled nicotine. Specific binding was calculated as the difference between {sup 3}H-nicotine bound in the presence and absence of unlabeled nicotine. The cells bound 1.44 (+/- 0.42) pmols/10(6) cells in the presence of unlabeled nicotine and 1.66 (+/- 0.55) pmols/10(6) cells in the absence of unlabeled nicotine. The difference was not significant. Uptake of nicotine was measured at 37{degree}C after treating cells with {sup 3}H-nicotine for time periods up to 4 hours. Uptake in pmols/10(6) cells was 4.90 (+/- 0.34) at 15 minutes, 8.30 (+/- 0.75) at 30 minutes, 12.28 (+/- 2.62) at 1 hour and 26.31 (+/- 1.15) at 4 hours.

  12. Cardiovascular toxicity of nicotine: Implications for electronic cigarette use.

    PubMed

    Benowitz, Neal L; Burbank, Andrea D

    2016-08-01

    The cardiovascular safety of nicotine is an important question in the current debate on the benefits vs. risks of electronic cigarettes and related public health policy. Nicotine exerts pharmacologic effects that could contribute to acute cardiovascular events and accelerated atherogenesis experienced by cigarette smokers. Studies of nicotine medications and smokeless tobacco indicate that the risks of nicotine without tobacco combustion products (cigarette smoke) are low compared to cigarette smoking, but are still of concern in people with cardiovascular disease. Electronic cigarettes deliver nicotine without combustion of tobacco and appear to pose low-cardiovascular risk, at least with short-term use, in healthy users. PMID:27079891

  13. Nicotine replacement therapies: patient safety and persistence

    PubMed Central

    Ferguson, Stuart G; Shiffman, Saul; Gitchell, Joseph G

    2011-01-01

    Nicotine replacement therapy (NRT) has become a central part of the treatment of nicotine dependence. However, NRT’s potential efficacy is limited to some extent by patient adherence and persistence. Here we review the relationship between NRT compliance and adherence, and overall treatment outcome. We then examine the factors that likely impact on treatment compliance and persistence, with a special focus on users’ perceptions of treatment safety and efficacy as possible mediators. Potential clinical strategies for improving suboptimal medication use are also discussed. PMID:22915971

  14. Complex suicide with homemade nicotine patches.

    PubMed

    Lardi, C; Vogt, S; Pollak, S; Thierauf, A

    2014-03-01

    Suicide by self-poisoning is rather common around the world. This paper presents an exceptional complex suicide in which nicotine was applied in the form of self-made patches soaked with an extraction from fine-cut tobacco. In addition, the 51-year-old suicide victim took a lethal dose of diphenhydramine. Toxicological analysis also revealed the presence of tetrazepam in subtherapeutic concentrations. The scene of death suggested an autoerotic accident at first, as the body was tied with tapes, cables and handcuffs. As a result of the entire investigations, the fatality had to be classified as a suicidal intoxication by nicotine and diphenhydramine. PMID:24439154

  15. Enhanced hydrogen storage properties of the 2LiBH4-MgH2 composite with BaTiO3 as an additive.

    PubMed

    Wang, Jiasheng; Han, Shumin; Wang, Zhibin; Ke, Dandan; Liu, Jingjing; Ma, Mingzhen

    2016-04-19

    The 2LiBH4-MgH2 + 20 wt% BaTiO3 composite was prepared by ball-milling LiBH4, MgH2 and BaTiO3, and the effect of BaTiO3 on the hydrogen storage properties of the composite was investigated. TG-DSC results show that the onset dehydrogenation temperature of the composite is 299 °C, which is 124 °C lower than that of 2LiBH4-MgH2, and the dehydrogenation amount of the composite increases from 6.86 wt% to 7.48 wt% at 500 °C. Kinetic tests show that the dehydrogenation amount of 2LiBH4-MgH2 + 20 wt% BaTiO3 reaches 1.5 wt% within 400 seconds, almost 10 times that of 2LiBH4-MgH2. BaTiO3 reacts with LiBH4 during the dehydrogenation of the composite and generates BaB6 and TiO2. BaB6 is beneficial to lower the stability of LiBH4, while TiO2 has a catalytic effect in improving the hydrogenation/dehydrogenation kinetics of the reaction between Mg and LiBH4. PMID:26990634

  16. Anxiogenic-like effects of chronic nicotine exposure in zebrafish.

    PubMed

    Stewart, Adam Michael; Grossman, Leah; Collier, Adam D; Echevarria, David J; Kalueff, Allan V

    2015-12-01

    Nicotine is one of the most widely used and abused legal drugs. Although its pharmacological profile has been extensively investigated in humans and rodents, nicotine CNS action remains poorly understood. The importance of finding evolutionarily conserved signaling pathways, and the need to apply high-throughput in vivo screens for CNS drug discovery, necessitate novel efficient experimental models for nicotine research. Zebrafish (Danio rerio) are rapidly emerging as an excellent organism for studying drug abuse, neuropharmacology and toxicology and have recently been applied to testing nicotine. Anxiolytic, rewarding and memory-modulating effects of acute nicotine treatment in zebrafish are consistently reported in the literature. However, while nicotine abuse is more relevant to long-term exposure models, little is known about chronic effects of nicotine on zebrafish behavior. In the present study, chronic 4-day exposure to 1-2mg/L nicotine mildly increased adult zebrafish shoaling but did not alter baseline cortisol levels. We also found that chronic exposure to nicotine evokes robust anxiogenic behavioral responses in zebrafish tested in the novel tank test paradigm. Generally paralleling clinical and rodent data on anxiogenic effects of chronic nicotine, our study supports the developing utility of zebrafish for nicotine research. PMID:25643654

  17. Discriminability of nicotine in tobacco smoke: implications for titration.

    PubMed

    Rose, J E

    1984-01-01

    Cigarette smokers were presented with puffs from either high (2.5 mg), medium (1.5 mg) or low (.5 mg) nicotine cigarettes in order to determine their ability to discriminate nicotine delivery in tobacco smoke. Puffs were presented in random order during each of two conditions and tar content was controlled by using research cigarettes and a smoke mixing device that varied only nicotine. The first condition allowed olfactory stimuli to be used in discrimination, while the second condition blocked olfaction by occluding subjects' nostrils. In both conditions, subjects discriminated between the nicotine content of different puffs, with higher nicotine puffs rated as significantly stronger (by roughly 50%). Subjective desirability ratings did not vary with nicotine delivery. The implications of the magnitude of change in subjects' ratings for theories of nicotine titration are discussed. PMID:6741679

  18. Cholinergic modulation of dopamine pathways through nicotinic acetylcholine receptors.

    PubMed

    de Kloet, Sybren F; Mansvelder, Huibert D; De Vries, Taco J

    2015-10-15

    Nicotine addiction is highly prevalent in current society and is often comorbid with other diseases. In the central nervous system, nicotine acts as an agonist for nicotinic acetylcholine receptors (nAChRs) and its effects depend on location and receptor composition. Although nicotinic receptors are found in most brain regions, many studies on addiction have focused on the mesolimbic system and its reported behavioral correlates such as reward processing and reinforcement learning. Profound modulatory cholinergic input from the pedunculopontine and laterodorsal tegmentum to dopaminergic midbrain nuclei as well as local cholinergic interneuron projections to dopamine neuron axons in the striatum may play a major role in the effects of nicotine. Moreover, an indirect mesocorticolimbic feedback loop involving the medial prefrontal cortex may be involved in behavioral characteristics of nicotine addiction. Therefore, this review will highlight current understanding of the effects of nicotine on the function of mesolimbic and mesocortical dopamine projections in the mesocorticolimbic circuit. PMID:26208783

  19. Structure of neat and hydrated liquid nicotine and laser resonant desorption of clusters from nicotine-water solutions

    NASA Astrophysics Data System (ADS)

    Mihesan, Claudia; Ziskind, Michael; Focsa, Cristian; Seydou, Mahamadou; Lecomte, Frédéric; Schermann, Jean Pierre

    2008-11-01

    The microscopic structures of neat liquid nicotine and nicotine-water mixtures are examined through infrared spectroscopy and laser resonant desorption mass-spectroscopy. The infrared spectra of the solutions are analyzed using DFT calculations of homogenous and mixed hydrogen-bonded clusters. Neat nicotine and hydrated nicotine cluster are experimentally observed through IR laser resonant desorption of a nicotine/water ice mixture followed by laser ionization mass-spectrometry. A sizable fraction of those cluster ions is the result of laser ionization of small neutral clusters already present in the sample.

  20. Nicotine delivery and pharmacologic response from Verve, an oral nicotine delivery product.

    PubMed

    Koszowski, Bartosz; Viray, Lauren C; Stanfill, Stephen B; Lisko, Joseph G; Rosenberry, Zach R; Potts, Jennifer L; Pickworth, Wallace B

    2015-09-01

    Verve, an oral nicotine delivery product (ONDP), was introduced by Nu Mark (Altria Client Group, Richmond VA) for smokers to use in places where smoking is prohibited. This study assessed the effect of this ONDP on plasma nicotine levels, heart rate, product satisfaction, and ability to suppress smoking urge and cigarette cravings. Thirteen daily cigarette smokers [8 men and 5 women; average age 33.4years] attended two laboratory sessions, one occurred after overnight tobacco abstinence. Plasma samples were collected before and after ONDP use and measured for nicotine. In non-abstinent smokers, mean plasma nicotine levels increased from 18.3 to 21.0ng/mL. In abstinent smokers, average nicotine levels increased from 3.1 to 4.5ng/mL. After overnight tobacco abstinence, ONDP use significantly (p<0.01) increased heart rate from 69beats per minute (bpm) to 75bpm; while urge to smoke decreased significantly (p<0.01) from a score of 8.6 to 4.9. Participants indicated moderate product satisfaction that was not changed by tobacco abstinence. Analysis of unused ONDP revealed total nicotine levels of 1.68±0.09mg/disc. Spent ONDP discs were also analyzed to determine % nicotine liberated during chewing; results were 80% in the non-abstinent and 82% in the abstinent conditions (ns). Our study results indicate that ONDP use can increase plasma nicotine levels and heart rate and reduce cigarette cravings in abstinent smokers. PMID:26096037

  1. REINFORCEMENT ENHANCING EFFECTS OF ACUTE NICOTINE VIA ELECTRONIC CIGARETTES

    PubMed Central

    Perkins, Kenneth A.; Karelitz, Joshua L.; Michael, Valerie C.

    2015-01-01

    Background Recent human studies confirm animal research showing that nicotine enhances reinforcement from rewards unrelated to nicotine. These effects of acute nicotine via tobacco smoking may also occur when consumed from non-tobacco products. Methods We assessed acute effects of nicotine via electronic cigarettes (“e-cigarettes”) on responding reinforced by music, video, or monetary rewards, or for no reward (control). In a fully within-subjects design, adult dependent smokers (N=28) participated in three similar experimental sessions, each following overnight abstinence (verified by CO≤10 ppm). Varying only in e-cigarette condition, sessions involved controlled exposure to a nicotine (labeled “36 mg/ml”) or placebo (“0”) e-cigarette, or no e-cigarette use. A fourth session involved smoking one’s own tobacco cigarette brand after no abstinence, specifically to compare responses under typical nicotine satiation with these acute e-cigarette conditions after abstinence. Results Reinforced responding for video reward, but not the other rewards, was greater due to use of the nicotine versus placebo e-cigarette (i.e., nicotine per se), while no differences were found between the placebo e-cigarette and no e-cigarette conditions (i.e., e-cigarette use per se). For nicotine via tobacco smoking, responding compared to the nicotine e-cigarette was similar for video but greater for music, while both video and music reward were enhanced relative to the non-nicotine conditions (placebo and no e-cigarette). Conclusions Acute nicotine from a non-tobacco product has some reinforcement enhancing effects in humans, in a manner partly consistent with nicotine via tobacco smoking and perhaps contributing to the rising popularity of nicotine e-cigarette use. PMID:26070455

  2. Nicotine, adolescence, and stress: A review of how stress can modulate the negative consequences of adolescent nicotine abuse.

    PubMed

    Holliday, Erica; Gould, Thomas J

    2016-06-01

    In order to continue the decline of smoking prevalence, it is imperative to identify factors that contribute to the development of nicotine and tobacco addiction, such as adolescent initiation of nicotine use, adolescent stress, and their interaction. This review highlights the biological differences between adolescent and adults in nicotine use and resulting effects, and examines the enduring consequences of adolescent nicotine administration. A review of both clinical and preclinical literature indicates that adolescent, but not adult, nicotine administration leads to increased susceptibility for development of long-lasting impairments in learning and affect. Finally, the role stress plays in normal adolescent development, the deleterious effects stress has on learning and memory, and the negative consequences resulting from the interaction of stress and nicotine during adolescence is reviewed. The review concludes with ways in which future policies could benefit by addressing adolescent stress as a means of reducing adolescent nicotine abuse. PMID:27068856

  3. Structural, Electronic and Elastic Properties of MgH2, CaH2 and Ca4Mg3H14 for Hydrogen Storage Materials

    NASA Astrophysics Data System (ADS)

    Djellab, Sihem; Bouhadda, Youcef; Bououdina, Mohamed; Fenineche, Noureddine; Boudouma, Youcef

    2016-08-01

    The structural, electronic and elastic properties of MgH2, CaH2 and Ca4Mg3H14 have been determined using first principles calculation based on density functional theory. The calculated lattice constants were in good agreement with the experimental values. The electronic density of states revealed that these hydrides are insulators. The calculated elastic constants of MgH2, CaH2 and Ca4Mg3H14 indicated that these hydrides are mechanically stable at zero pressure. The bulk modulus B, shear modulus G, Young's modulus E, and Poisson's ratio ν were derived, and the ductility was discussed.

  4. Nicotinic Acetylcholine Receptors in Sensory Cortex

    ERIC Educational Resources Information Center

    Metherate, Raju

    2004-01-01

    Acetylcholine release in sensory neocortex contributes to higher-order sensory function, in part by activating nicotinic acetylcholine receptors (nAChRs). Molecular studies have revealed a bewildering array of nAChR subtypes and cellular actions; however, there is some consensus emerging about the major nAChR subtypes and their functions in…

  5. Many Teens 'Vaping' for Flavor, Not Nicotine

    MedlinePlus

    ... always known nor do they appear on the product labels," she said. "Consequently, I would have thought that there would be more teens reporting that they did not know what substances they ... nicotine, inhaled products that contain flavorings can be damaging to the ...

  6. R-Modafinil Attenuates Nicotine-Taking and Nicotine-Seeking Behavior in Alcohol-Preferring Rats

    PubMed Central

    Wang, Xiao-Fei; Bi, Guo-Hua; He, Yi; Yang, Hong-Ju; Gao, Jun-Tao; Okunola-Bakare, Oluyomi M; Slack, Rachel D; Gardner, Eliot L; Xi, Zheng-Xiong; Newman, Amy Hauck

    2015-01-01

    (±)-Modafinil (MOD) is used clinically for the treatment of sleep disorders and has been investigated as a potential medication for the treatment of psychostimulant addiction. However, the therapeutic efficacy of (±)-MOD for addiction is inconclusive. Herein we used animal models of self-administration and in vivo microdialysis to study the pharmacological actions of R-modafinil (R-MOD) and S-modafinil (S-MOD) on nicotine-taking and nicotine-seeking behavior, and mechanisms underlying such actions. We found that R-MOD is more potent and effective than S-MOD in attenuating nicotine self-administration in Long–Evans rats. As Long–Evans rats did not show a robust reinstatement response to nicotine, we used alcohol-preferring rats (P-rats) that display much higher reinstatement responses to nicotine than Long–Evans rats. We found that R-MOD significantly inhibited intravenous nicotine self-administration, nicotine-induced reinstatement, and nicotine-associated cue-induced drug-seeking behavior in P-rats. R-MOD alone neither sustained self-administration in P-rats previously self-administering nicotine nor reinstated extinguished nicotine-seeking behavior. The in vivo brain microdialysis assays demonstrated that R-MOD alone produced a slow-onset moderate increase in extracellular DA. Pretreatment with R-MOD dose-dependently blocked nicotine-induced dopamine (DA) release in the nucleus accumbens (NAc) in both naive and nicotine self-administrating rats, suggesting a DA-dependent mechanism underlying mitigation of nicotine's effects. In conclusion, the present findings support further investigation of R-MOD for treatment of nicotine dependence in humans. PMID:25613829

  7. Curcumin improves liver damage in male mice exposed to nicotine

    PubMed Central

    Salahshoor, Mohammadreza; Mohamadian, Sabah; Kakabaraei, Seyran; Roshankhah, Shiva; Jalili, Cyrus

    2015-01-01

    The color of turmeric (薑黃 jiāng huáng) is because of a substance called curcumin. It has different pharmacological effects, such as antioxidant and anti-inflammatory properties. Nicotine is a major pharmacologically active substance in cigarette smoke. It is mainly metabolized in the liver and causes devastating effects. This study was designed to evaluate the protective role of curcumin against nicotine on the liver in mice. Forty-eight mice were equally divided into eight groups; control (normal saline), nicotine (2.5 mg/kg), curcumin (10, 30, and 60 mg/kg) and curcumin plus nicotine-treated groups. Curcumin, nicotine, and curcumin plus nicotine (once a day) were intraperitoneally injected for 4 weeks. The liver weight and histology, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and serum nitric oxide levels have been studied. The results indicated that nicotine administration significantly decreased liver weight and increased the mean diameter of hepatocyte, central hepatic vein, liver enzymes level, and blood serum nitric oxide level compared with the saline group (p < 0.05). However, curcumin and curcumin plus nicotine administration substantially increased liver weight and decreased the mean diameter of hepatocyte, central hepatic vein, liver enzymes, and nitric oxide levels in all groups compared with the nicotine group (p < 0.05). Curcumin demonstrated its protective effect against nicotine-induced liver toxicity. PMID:27114942

  8. Curcumin improves liver damage in male mice exposed to nicotine.

    PubMed

    Salahshoor, Mohammadreza; Mohamadian, Sabah; Kakabaraei, Seyran; Roshankhah, Shiva; Jalili, Cyrus

    2016-04-01

    The color of turmeric ( jiāng huáng) is because of a substance called curcumin. It has different pharmacological effects, such as antioxidant and anti-inflammatory properties. Nicotine is a major pharmacologically active substance in cigarette smoke. It is mainly metabolized in the liver and causes devastating effects. This study was designed to evaluate the protective role of curcumin against nicotine on the liver in mice. Forty-eight mice were equally divided into eight groups; control (normal saline), nicotine (2.5 mg/kg), curcumin (10, 30, and 60 mg/kg) and curcumin plus nicotine-treated groups. Curcumin, nicotine, and curcumin plus nicotine (once a day) were intraperitoneally injected for 4 weeks. The liver weight and histology, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and serum nitric oxide levels have been studied. The results indicated that nicotine administration significantly decreased liver weight and increased the mean diameter of hepatocyte, central hepatic vein, liver enzymes level, and blood serum nitric oxide level compared with the saline group (p < 0.05). However, curcumin and curcumin plus nicotine administration substantially increased liver weight and decreased the mean diameter of hepatocyte, central hepatic vein, liver enzymes, and nitric oxide levels in all groups compared with the nicotine group (p < 0.05). Curcumin demonstrated its protective effect against nicotine-induced liver toxicity. PMID:27114942

  9. Nicotine administration enhances negative occasion setting in adolescent rats.

    PubMed

    Meyer, Heidi C; Chodakewitz, Molly I; Bucci, David J

    2016-04-01

    Substantial research has established that exposure to nicotine during adolescence can lead to long-term changes in neural circuitry and behavior. However, relatively few studies have considered the effects of nicotine use on cognition during this critical stage of brain development. This is significant because the influence of nicotine on cognitive performance during adolescence may contribute to the development of regular nicotine use. For example, improvements in cognitive functioning may increase the perceived value of smoking and facilitate impulses to smoke. To address this, the present research tested the effects of nicotine on a form of inhibitory learning during adolescence. Specifically, adolescent rats were exposed to nicotine as they were trained in a negative occasion setting paradigm, in which successful performance depends on learning the conditions under which it is, or is not, appropriate to respond to a target stimulus. Here, we found that nicotine administration enhances negative occasion setting in adolescents. In addition, nicotine increased the amount of orienting behavior directed toward the inhibitory stimulus, suggesting that improvements in this form of behavioral inhibition may be attributed to nicotine-induced increases in attentional processing. These results may help elucidate the factors that contribute to the onset as well as continued use of products containing nicotine during adolescence and provide insight to increase the effectiveness of interventions targeted at reducing the prevalence of adolescent smoking. PMID:26779671

  10. Opioid Analgesics and Nicotine: More Than Blowing Smoke.

    PubMed

    Yoon, Jin H; Lane, Scott D; Weaver, Michael F

    2015-09-01

    Practitioners are highly likely to encounter patients with concurrent use of nicotine products and opioid analgesics. Smokers present with more severe and extended chronic pain outcomes and have a higher frequency of prescription opioid use. Current tobacco smoking is a strong predictor of risk for nonmedical use of prescription opioids. Opioid and nicotinic-cholinergic neurotransmitter systems interact in important ways to modulate opioid and nicotine effects: dopamine release induced by nicotine is dependent on facilitation by the opioid system, and the nicotinic-acetylcholine system modulates self-administration of several classes of abused drugs-including opioids. Nicotine can serve as a prime for the use of other drugs, which in the case of the opioid system may be bidirectional. Opioids and compounds in tobacco, including nicotine, are metabolized by the cytochrome P450 enzyme system, but the metabolism of opioids and tobacco products can be complicated. Accordingly, drug interactions are possible but not always clear. Because of these issues, asking about nicotine use in patients taking opioids for pain is recommended. When assessing patient tobacco use, practitioners should also obtain information on products other than cigarettes, such as cigars, pipes, smokeless tobacco, and electronic nicotine delivery systems (ENDS, or e-cigarettes). There are multiple forms of behavioral therapy and pharmacotherapy available to assist patients with smoking cessation, and opioid agonist maintenance and pain clinics represent underutilized opportunities for nicotine intervention programs. PMID:26375198

  11. Chronic Nicotine Exposure Attenuates Methamphetamine-Induced Dopaminergic Deficits.

    PubMed

    Vieira-Brock, Paula L; McFadden, Lisa M; Nielsen, Shannon M; Ellis, Jonathan D; Walters, Elliot T; Stout, Kristen A; McIntosh, J Michael; Wilkins, Diana G; Hanson, Glen R; Fleckenstein, Annette E

    2015-12-01

    Repeated methamphetamine (METH) administrations cause persistent dopaminergic deficits resembling aspects of Parkinson's disease. Many METH abusers smoke cigarettes and thus self-administer nicotine; yet few studies have investigated the effects of nicotine on METH-induced dopaminergic deficits. This interaction is of interest because preclinical studies demonstrate that nicotine can be neuroprotective, perhaps owing to effects involving α4β2 and α6β2 nicotinic acetylcholine receptors (nAChRs). This study revealed that oral nicotine exposure beginning in adolescence [postnatal day (PND) 40] through adulthood [PND 96] attenuated METH-induced striatal dopaminergic deficits when METH was administered at PND 89. This protection did not appear to be due to nicotine-induced alterations in METH pharmacokinetics. Short-term (i.e., 21-day) high-dose nicotine exposure also protected when administered from PND 40 to PND 61 (with METH at PND 54), but this protective effect did not persist. Short-term (i.e., 21-day) high-dose nicotine exposure did not protect when administered postadolescence (i.e., beginning at PND 61, with METH at PND 75). However, protection was engendered if the duration of nicotine exposure was extended to 39 days (with METH at PND 93). Autoradiographic analysis revealed that nicotine increased striatal α4β2 expression, as assessed using [(125)I]epibatidine. Both METH and nicotine decreased striatal α6β2 expression, as assessed using [(125)I]α-conotoxin MII. These findings indicate that nicotine protects against METH-induced striatal dopaminergic deficits, perhaps by affecting α4β2 and/or α6β2 expression, and that both age of onset and duration of nicotine exposure affect this protection. PMID:26391161

  12. Nicotine increases GABAergic input on rat dorsal raphe serotonergic neurons through alpha7 nicotinic acetylcholine receptor.

    PubMed

    Hernández-Vázquez, F; Chavarría, K; Garduño, J; Hernández-López, S; Mihailescu, S P

    2014-12-15

    The dorsal raphe nucleus (DRN) contains large populations of serotonergic (5-HT) neurons. This nucleus receives GABAergic inhibitory afferents from many brain areas and from DRN interneurons. Both GABAergic and 5-HT DRN neurons express functional nicotinic acetylcholine receptors (nAChRs). Previous studies have demonstrated that nicotine increases 5-HT release and 5-HT DRN neuron discharge rate by stimulating postsynaptic nAChRs and by increasing glutamate and norepinephrine release inside DRN. However, the influence of nicotine on the GABAergic input to 5-HT DRN neurons was poorly investigated. Therefore, the aim of this work was to determine the effect of nicotine on GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) of 5-HT DRN neurons and the subtype of nAChR(s) involved in this response. Experiments were performed in coronal slices obtained from young Wistar rats. GABAergic sIPSCs were recorded from post hoc-identified 5-HT DRN neurons with the whole cell voltage patch-clamp technique. Administration of nicotine (1 μM) increased sIPSC frequency in 72% of identified 5-HT DRN neurons. This effect was not reproduced by the α4β2 nAChR agonist RJR-2403 and was not influenced by TTX (1 μM). It was mimicked by the selective agonist for α7 nAChR, PNU-282987, and exacerbated by the positive allosteric modulator of the same receptor, PNU-120596. The nicotine-induced increase in sIPSC frequency was independent on voltage-gated calcium channels and dependent on Ca(2+)-induced Ca(2+) release (CICR). These results demonstrate that nicotine increases the GABAergic input to most 5-HT DRN neurons, by activating α7 nAChRs and producing CICR in DRN GABAergic terminals. PMID:25231613

  13. Multiple cholinergic nicotinic receptor genes affect nicotine dependence risk in African and European Americans

    PubMed Central

    Saccone, Nancy L.; Schwantes-An, Tae-Hwi; Wang, Jen C.; Grucza, Richard A.; Breslau, Naomi; Hatsukami, Dorothy; Johnson, Eric O.; Rice, John P.; Goate, Alison M.; Bierut, Laura J.

    2010-01-01

    Several independent studies show that the chromosome 15q25.1 region, which contains the CHRNA5-CHRNA3-CHRNB4 gene cluster, harbors variants strongly associated with nicotine dependence, other smoking behaviors, lung cancer, and chronic obstructive pulmonary disease. We investigated whether variants in other cholinergic nicotinic receptor subunit (CHRN) genes affect risk for nicotine dependence in a new sample of African-Americans (N = 710). We also analyzed this African-American sample together with a European-American sample (N=2062, 1608 of which have been previously studied), allowing for differing effects in the two populations. Cases are current nicotine-dependent smokers and controls are non-dependent smokers. Variants in or near CHRND-CHRNG, CHRNA7, and CHRNA10 show modest association with nicotine dependence risk in the African-American sample. In addition, CHRNA4, CHRNB3-CHRNA6, and CHRNB1 show association in at least one population. CHRNG and CHRNA4 harbor SNPs that have opposite directions of effect in the two populations. In each of the population samples, these loci substantially increase the trait variation explained, although no loci meet Bonferroni-corrected significance in the African-American sample alone. The trait variation explained by three key associated SNPs in CHRNA5-CHRNA3-CHRNB4 is 1.9% in European-Americans and also 1.9% in African-Americans; this increases to 4.5% in EAs and 7.3% in AAs when we add six variants representing associations at other CHRN genes. Multiple nicotinic receptor subunit genes outside of chromosome 15q25 are likely to be important in the biological processes and development of nicotine dependence, and some of these risks may be shared across diverse populations. PMID:20584212

  14. The Sensory Impact of Nicotine on Noradrenergic and Dopaminergic Neurons of the Nicotine Reward - Addiction Neurocircuitry

    PubMed Central

    Rose, Jed E; Dehkordi, Ozra; Manaye, Kebreten F; Millis, Richard M; Cianaki, Salman Ameri; Jayam-Trouth, Annapurni

    2016-01-01

    The sensory experience of smoking is a key component of nicotine addiction known to result, in part, from stimulation of nicotinic acetylcholine receptors (nAChRs) at peripheral sensory nerve endings. Such stimulation of nAChRs is followed by activation of neurons at multiple sites in the mesocorticolimbic reward pathways. However, the neurochemical profiles of CNS cells that mediate the peripheral sensory impact of nicotine remain unknown. In the present study in mice, we first used c-Fos immunohistochemistry to identify CNS cells stimulated by nicotine (NIC, 40 μg/kg, IP) and by a peripherally-acting analog of nicotine, nicotine pyrrolidine methiodide (NIC-PM, 30 μg/kg, IP). Sequential double-labelling was then performed to determine whether noradrenergic and dopaminergic neurons of the nicotine reward-addiction circuitry were primary targets of NIC and NIC-PM. Double-labelling of NIC and/or NIC-PM activated c-Fos immunoreactive cells with tyrosine hydroxylase (TH) showed no apparent c-Fos expression by the dopaminergic cells of the ventral tegmental area (VTA). With the exception of sparse numbers of TH immunoreactive D11 cells, dopamine-containing neurons in other areas of the reward-addiction circuitry, namely periaqueductal gray, and dorsal raphe, were also devoid of c-Fos immunoreactivity. Noradrenergic neurons of locus coeruleus (LC), known to innervate VTA, were activated by both NIC and NIC-PM. These results demonstrate that noradrenergic neurons of LC are among the first structures that are stimulated by single acute IP injection of NIC and NIC-PM. Dopaminergic neurons of VTA and other CNS sites, did not respond to acute IP administration of NIC or NIC-PM by induction of c-Fos. PMID:27347434

  15. Neuronal Nicotinic Acetylcholine Receptors: Common Molecular Substrates of Nicotine and Alcohol Dependence

    PubMed Central

    Hendrickson, Linzy M.; Guildford, Melissa J.; Tapper, Andrew R.

    2013-01-01

    Alcohol and nicotine are often co-abused. As many as 80–95% of alcoholics are also smokers, suggesting that ethanol and nicotine, the primary addictive component of tobacco smoke, may functionally interact in the central nervous system and/or share a common mechanism of action. While nicotine initiates dependence by binding to and activating neuronal nicotinic acetylcholine receptors (nAChRs), ligand-gated cation channels normally activated by endogenous acetylcholine (ACh), ethanol is much less specific with the ability to modulate multiple gene products including those encoding voltage-gated ion channels, and excitatory/inhibitory neurotransmitter receptors. However, emerging data indicate that ethanol interacts with nAChRs, both directly and indirectly, in the mesocorticolimbic dopaminergic (DAergic) reward circuitry to affect brain reward systems. Like nicotine, ethanol activates DAergic neurons of the ventral tegmental area (VTA) which project to the nucleus accumbens (NAc). Blockade of VTA nAChRs reduces ethanol-mediated activation of DAergic neurons, NAc DA release, consumption, and operant responding for ethanol in rodents. Thus, ethanol may increase ACh release into the VTA driving activation of DAergic neurons through nAChRs. In addition, ethanol potentiates distinct nAChR subtype responses to ACh and nicotine in vitro and in DAergic neurons. The smoking cessation therapeutic and nAChR partial agonist, varenicline, reduces alcohol consumption in heavy drinking smokers and rodent models of alcohol consumption. Finally, single nucleotide polymorphisms in nAChR subunit genes are associated with alcohol dependence phenotypes and smoking behaviors in human populations. Together, results from pre-clinical, clinical, and genetic studies indicate that nAChRs may have an inherent role in the abusive properties of ethanol, as well as in nicotine and alcohol co-dependence. PMID:23641218

  16. A Multi-Route Model of Nicotine-Cotinine Pharmacokinetics, Pharmacodynamics and Brain Nicotinic Acetylcholine Receptor Binding in Humans

    SciTech Connect

    Teeguarden, Justin G.; Housand, Conrad; Smith, Jordan N.; Hinderliter, Paul M.; Gunawan, Rudy; Timchalk, Charles

    2013-02-01

    The pharmacokinetics of nicotine, the pharmacologically active alkaloid in tobacco responsible for addiction, are well characterized in humans. We developed a physiologically based pharmacokinetic/pharmacodynamic model of nicotine pharmacokinetics, brain dosimetry and brain nicotinic acetylcholine receptor (nAChRs) occupancy. A Bayesian framework was applied to optimize model parameters against multiple human data sets. The resulting model was consistent with both calibration and test data sets, but in general underestimated variability. A pharmacodynamic model relating nicotine levels to increases in heart rate as a proxy for the pharmacological effects of nicotine accurately described the nicotine related changes in heart rate and the development and decay of tolerance to nicotine. The PBPK model was utilized to quantitatively capture the combined impact of variation in physiological and metabolic parameters, nicotine availability and smoking compensation on the change in number of cigarettes smoked and toxicant exposure in a population of 10,000 people presented with a reduced toxicant (50%), reduced nicotine (50%) cigarette Across the population, toxicant exposure is reduced in some but not all smokers. Reductions are not in proportion to reductions in toxicant yields, largely due to partial compensation in response to reduced nicotine yields. This framework can be used as a key element of a dosimetry-driven risk assessment strategy for cigarette smoke constituents.

  17. Nicotinic Mechanisms Modulate Ethanol Withdrawal and Modify Time Course and Symptoms Severity of Simultaneous Withdrawal from Alcohol and Nicotine.

    PubMed

    Perez, Erika; Quijano-Cardé, Natalia; De Biasi, Mariella

    2015-09-01

    Alcohol and nicotine are among the top causes of preventable death in the United States. Unfortunately, people who are dependent on alcohol are more likely to smoke than individuals in the general population. Similarly, smokers are more likely to abuse alcohol. Alcohol and nicotine codependence affects health in many ways and leads to poorer treatment outcomes in subjects who want to quit. This study examined the interaction of alcohol and nicotine during withdrawal and compared abstinence symptoms during withdrawal from one of the two drugs only vs both. Our results indicate that simultaneous withdrawal from alcohol and nicotine produces physical symptoms that are more severe and last longer than those experienced during withdrawal from one of the two drugs alone. In animals experiencing withdrawal after chronic ethanol treatment, acute nicotine exposure was sufficient to prevent abstinence symptoms. Similarly, symptoms were prevented when alcohol was injected acutely in mice undergoing nicotine withdrawal. These experiments provide evidence for the involvement of the nicotinic cholinergic system in alcohol withdrawal. Furthermore, the outcomes of intracranial microinfusions of mecamylamine, a nonselective nicotinic receptor antagonist, highlight a major role for the nicotinic receptors expressed in medial habenula and interpeduncular nucleus during withdrawal. Overall, the data support the notion that modulating the nicotinic cholinergic system might help to maintain long-term abstinence from alcohol. PMID:25790020

  18. Biodegradation of nicotine by a newly isolated Pseudomonas stutzeri JZD

    NASA Astrophysics Data System (ADS)

    Petricevic, Jelena; Gujanicic, Vera; Radic, Danka; Jovicic Petrovic, Jelena; Jovic, Jelena; Raicevic, Vera

    2013-04-01

    The tobacco-manufacturing process and all activities that use tobacco, produce solid or liquid wastes with high concentrations of nicotine. Nicotine is a significant toxic waste product in tobacco industry. This waste is classified as 'toxic and hazardous' by European Union regulations when the nicotine content exceeds 500 milligrams per kilogram dry weight. Therefore, there is a major environmental requirement to remove nicotine from tobacco wastes. Bioremediation techniques which involve nicotine degradation by microorganisms have attracted attention during the last years, because microorganisms have the potential to reduce nicotine levels in tobacco and to detoxify tobacco wastes. The aim of this study is isolation and identification of nicotine degraded bacteria and optimization of nicotine degradation in laboratory conditions. An aerobic bacterial strain capable of effectively degrading nicotine was isolated from the tobacco industry waste, Serbia. After isolation, the liquid culture was spread onto the solid plates of the nicotine inorganic salt medium using the dilution plate method. Cell morphology of strain was observed by a light microscope and physiological characteristics were determined by Api technique and sequence analyzes of 16S rDNA. This isolate was identified as Pseudomonas stutzeri based on morphology, physiological characteristics, and Apiweb technique. Comparison with sequences available in data library showed the 99% similarity with 16S rDNA gene sequence of the species Pseudomonas stutzeri ( GenBank Acc. No. CP003725). We analyzed the effect of initial nicotine concentration (1g/L, 1.5 g/L, 2.5 g/L) on microbial activity in aim to optimize biodegradation. The effect of cultivation temperature (25°C; 30°C; 37°C) on nicotine degradation by P. stutzeri was evaluated after 24 h of cultivation, with 1.5 g/L nicotine added as the sole carbon source. Effect of biodegradation has depended on initial concentration. During incubation, number of

  19. The role of nicotinic acid metabolites in flushing and hepatotoxicity.

    PubMed

    Stern, Ralph H

    2007-07-01

    Flushing and hepatotoxicity are important adverse effects of nicotinic acid. This article reviews the role of metabolism of nicotinic acid in the production of these side effects. The suggestion that nicotinic acid (NUA) formation produces flushing is traced to a correlation of flushing with NUA C(max) (maximal concentration) and the observation that aspirin inhibits NUA formation and flushing. The former does not establish causation and the latter can be explained by inhibition of prostaglandin formation. Recent characterization of the GPR109A receptor that mediates prostaglandin release by Langerhans cells to produce flushing has shown nicotinic acid, not NUA, is responsible. The suggestion that nicotinamide metabolites produce hepatotoxicity is not supported by any data. The mechanism of hepatotoxicity is unknown and a toxic metabolite of nicotinic acid has not been identified. Different nicotinic acid formulations produce different metabolite patterns due to nonlinear pharmacokinetics, but there is no evidence that these differences have any clinical importance. PMID:21291680

  20. In vivo and in vitro alteration of nicotine metabolism by the major metabolite of phenytoin.

    PubMed

    Lubawy, W C; Kostenbauder, H B; McGovren, J P

    1978-02-01

    The influence of hydroxyphentoin (HPPH), the major metabolite of phenytoin, on the in vitro and in vivo metabolism of nicotine was examined. In rat liver 9,000 g supernatant HPPH decreased the appearance of cotinine from nicotine by 65% while not influencing the disappearance of nicotine or the appearance of nicotine-l'-N-oxide. In vivo, HPPH inhibited both nicotine elimination and cotinine formation but did not affect nicotin-l'-N-oxide formation. PMID:25464

  1. Neuronal nicotinic acetylcholine receptors: neuroplastic changes underlying alcohol and nicotine addictions

    PubMed Central

    Feduccia, Allison A.; Chatterjee, Susmita; Bartlett, Selena E.

    2012-01-01

    Addictive drugs can activate systems involved in normal reward-related learning, creating long-lasting memories of the drug's reinforcing effects and the environmental cues surrounding the experience. These memories significantly contribute to the maintenance of compulsive drug use as well as cue-induced relapse which can occur even after long periods of abstinence. Synaptic plasticity is thought to be a prominent molecular mechanism underlying drug-induced learning and memories. Ethanol and nicotine are both widely abused drugs that share a common molecular target in the brain, the neuronal nicotinic acetylcholine receptors (nAChRs). The nAChRs are ligand-gated ion channels that are vastly distributed throughout the brain and play a key role in synaptic neurotransmission. In this review, we will delineate the role of nAChRs in the development of ethanol and nicotine addiction. We will characterize both ethanol and nicotine's effects on nAChR-mediated synaptic transmission and plasticity in several key brain areas that are important for addiction. Finally, we will discuss some of the behavioral outcomes of drug-induced synaptic plasticity in animal models. An understanding of the molecular and cellular changes that occur following administration of ethanol and nicotine will lead to better therapeutic strategies. PMID:22876217

  2. Cellular Basis for the Olfactory Response to Nicotine

    PubMed Central

    2010-01-01

    Smokers regulate their smoking behavior on the basis of sensory stimuli independently of the pharmacological effects of nicotine (RoseJ. E., et al. (1993) Pharmacol., Biochem. Behav.1 (3), 891−9008469698). A better understanding of sensory mechanisms underlying smoking behavior may help to develop more effective smoking alternatives. Olfactory stimulation by nicotine makes up a considerable part of the flavor of tobacco smoke, yet our understanding of the cellular mechanisms responsible for olfactory detection of nicotine remains incomplete. We used biophysical methods to characterize the nicotine sensitivity and response mechanisms of neurons from olfactory epithelium. In view of substantial differences in the olfactory receptor repertoire between rodent and human (MombaertsP. (1999) Annu. Rev. Neurosci.1, 487−50910202546), we studied biopsied human olfactory sensory neurons (OSNs), cultured human olfactory cells (GomezG., et al. (2000) J. Neurosci. Res.1 (3), 737−74911104513), and rat olfactory neurons. Rat and human OSNs responded to S(−)-nicotine with a concentration dependent influx of calcium and activation of adenylate cyclase. Some rat OSNs displayed some stereoselectivity, with neurons responding to either enantiomer alone or to both. Freshly biopsied and primary cultured human olfactory neurons were less stereoselective. Nicotinic cholinergic antagonists had no effect on the responses of rat or human OSNs to nicotine. Patch clamp recording of rat OSNs revealed a nicotine-activated, calcium-sensitive nonspecific cation channel. These results indicate that nicotine activates a canonical olfactory receptor pathway rather than nicotinic cholinergic receptors on OSNs. Further, because the nicotine-sensitive mechanisms of rodents appear generally similar to those of humans, this animal model is an appropriate one for studies of nicotine sensation. PMID:22777075

  3. Harm perception of nicotine products in college freshmen.

    PubMed

    Smith, Stephanie Y; Curbow, Barbara; Stillman, Frances A

    2007-09-01

    This study examined the association of sociodemographic characteristics and smoking behaviors (i.e., cigarette, cigar, and waterpipe) with nicotine product harm perception in college freshmen. Students were asked to compare the perceived harmfulness of 11 nicotine-delivering products with that of a regular cigarette. Data were from a cross-sectional Internet survey conducted during the spring 2004 semester at a private university (N = 411). Binomial logistic regression was used to determine the association between sociodemographic and behavioral factors with nicotine product harm perception. A statistically significant association was found between nicotine product harm perception and sex, race, income, citizenship, and smoking behavior (p< or =.05). Regarding the three medicinal nicotine replacement therapies, 19.6% of respondents incorrectly perceived the nicotine patch to be as harmful as or more harmful than a regular cigarette; corresponding values were 24.1% for nicotine gum and 52.9% for nicotine inhaler. Respondents incorrectly perceived the following smoked tobacco products to be less harmful than regular cigarettes: ultra-light cigarettes (40.4%), waterpipe (37%), light cigarettes (35.2%), cigarillos (17.4%), and cigars (16.9%). Regarding smokeless nicotine products, 89.3% of respondents incorrectly perceived dip and chew to be as harmful as or more harmful than regular cigarettes; corresponding values were 36.2% for nicotine lollipops and 35.2% for nicotine water. Our findings reveal misperceptions about nicotine product harmfulness and underscore the importance of developing a science base to inform policies and educate consumers about these products. PMID:17763115

  4. Cellular basis for the olfactory response to nicotine.

    PubMed

    Bryant, Bruce; Xu, Jiang; Audige, Valery; Lischka, Fritz W; Rawson, Nancy E

    2010-03-17

    Smokers regulate their smoking behavior on the basis of sensory stimuli independently of the pharmacological effects of nicotine (Rose J. E., et al. (1993) Pharmacol., Biochem. Behav.44 (4), 891-900). A better understanding of sensory mechanisms underlying smoking behavior may help to develop more effective smoking alternatives. Olfactory stimulation by nicotine makes up a considerable part of the flavor of tobacco smoke, yet our understanding of the cellular mechanisms responsible for olfactory detection of nicotine remains incomplete. We used biophysical methods to characterize the nicotine sensitivity and response mechanisms of neurons from olfactory epithelium. In view of substantial differences in the olfactory receptor repertoire between rodent and human (Mombaerts P. (1999) Annu. Rev. Neurosci.22, 487-509), we studied biopsied human olfactory sensory neurons (OSNs), cultured human olfactory cells (Gomez G., et al. (2000) J. Neurosci. Res.62 (5), 737-749), and rat olfactory neurons. Rat and human OSNs responded to S(-)-nicotine with a concentration dependent influx of calcium and activation of adenylate cyclase. Some rat OSNs displayed some stereoselectivity, with neurons responding to either enantiomer alone or to both. Freshly biopsied and primary cultured human olfactory neurons were less stereoselective. Nicotinic cholinergic antagonists had no effect on the responses of rat or human OSNs to nicotine. Patch clamp recording of rat OSNs revealed a nicotine-activated, calcium-sensitive nonspecific cation channel. These results indicate that nicotine activates a canonical olfactory receptor pathway rather than nicotinic cholinergic receptors on OSNs. Further, because the nicotine-sensitive mechanisms of rodents appear generally similar to those of humans, this animal model is an appropriate one for studies of nicotine sensation. PMID:22777075

  5. Revisiting the Effect of Nicotine on Interval Timing

    PubMed Central

    Daniels, Carter W.; Watterson, Elizabeth; Garcia, Raul; Mazur, Gabriel J.; Brackney, Ryan J.; Sanabria, Federico

    2015-01-01

    This paper reviews the evidence for nicotine-induced acceleration of the internal clock when timing in the seconds-to-minutes timescale, and proposes an alternative explanation to this evidence: that nicotine reduces the threshold for responses that result in more reinforcement. These two hypotheses were tested in male Wistar rats using a novel timing task. In this task, rats were trained to seek food at one location after 8 s since trial onset and at a different location after 16 s. Some rats received the same reward at both times (group SAME); some received a larger reward at 16 s (group DIFF). Steady baseline performance was followed by 3 days of subcutaneous nicotine administration (0.3 mg/kg), baseline recovery, and an antagonist challenge (mecamylamine, 1.0 mg/kg). Nicotine induced a larger, immediate reduction in latencies to switch (LTS) in group DIFF than in group SAME. This effect was sustained throughout nicotine administration. Mecamylamine administration and discontinuation of nicotine rapidly recovered baseline performance. These results support a response-threshold account of nicotinic disruption of timing performance, possibly mediated by nicotinic acetylcholine receptors. A detailed analysis of the distribution of LTSs suggests that anomalous effects of nicotine on LTS dispersion may be due to loss of temporal control of behavior. PMID:25637907

  6. A two-injection protocol for nicotine sensitization.

    PubMed

    Bernardi, Rick E; Spanagel, Rainer

    2014-12-15

    Sensitization to the locomotor activating effect of drugs of abuse occurs following repeated exposure to a drug, and/or when limited exposure to a drug is paired with a specific environment. Conditioned, or context-dependent, sensitization has been well-characterized using limited exposure protocols in, for example, cocaine- and amphetamine-treated animals. However, little data exists regarding limited exposure protocols for other drugs of abuse, such as nicotine. The current experiment investigated whether a two-injection protocol of nicotine administration would result in locomotor sensitization. Mice administered two injections of nicotine (0.175mg/kg, s.c.) 7d apart demonstrated significant locomotor sensitization in response to the second exposure. Furthermore, the development of this sensitization was blocked by the administration of the nicotinic acetylcholine receptor antagonist mecamylamine (2mg/kg) prior to the first nicotine exposure. In a follow-up study, we found that this two-injection nicotine sensitization was independent of context, as separate groups of mice given an initial nicotine exposure (0.175mg/kg, s.c.) in either the specific environment in which locomotor activity was tested or in their home cages demonstrated equivalent levels of locomotor activity during subsequent testing 7d later. These data suggest a novel approach to nicotine sensitization using limited nicotine exposure. PMID:25192633

  7. Nicotinic modulation of serotonergic activity in the dorsal raphe nucleus.

    PubMed

    Hernandez-Lopez, Salvador; Garduño, Julieta; Mihailescu, Stefan

    2013-01-01

    Cholinergic signaling mediated by nicotinic receptors has been associated to a large number of physiological and behavioral processes such as learning, memory, attention, food-intake and mood disorders. Although it is well established that many nicotinic actions are mediated through an increase in serotonin (5-HT) release, the physiological mechanisms by which nicotine produces these effects are still unclear. The dorsal raphe nucleus (DRN) contains the major amount of 5-HT neurons projecting to different parts of the brain. DRN also contains nicotinic acetylcholine receptors (nAChRs) located at somatic and presynaptic elements. Nicotine produces both inhibitory and excitatory effects on different subpopulations of 5-HT DRN neurons. In this review, we describe the presynaptic and postsynaptic mechanisms by which nicotine increases the excitability of DRN neurons as well as the subtypes of nAChRs involved. We also describe the inhibitory effects of nicotine and the role of 5-HT1A receptors in this effect. These nicotinic actions modulate the activity of different neuronal subpopulations in the DRN, changing the 5-HT tone in the brain areas where these groups of neurons project. Some of the physiological implications of nicotine-induced 5-HT release are discussed. PMID:24021594

  8. In vitro study of nicotine release from smokeless tobacco.

    PubMed

    Nasr, M M; Reepmeyer, J C; Tang, Y

    1998-01-01

    Four brands (Copenhagen Snuff, Skoal Bandit Classic, Skoal Wintergreen Long Cut, and Skoal Wintergreen Fine Cut) of smokeless tobacco products were tested for their rate of nicotine release into artificial saliva via direct contact or through a dialysis bag. Nicotine was determined by reversed-phase liquid chromatography. When samples were in direct contact with artificial saliva, most of the nicotine was released from the tobacco in the first minute. Nicotine release from Skoal Bandit Classic, marketed as smokeless tobacco in a sachet, was slower with the sachet intact than without the sachet. When smokeless tobacco and artificial saliva were placed inside a dialysis bag, nicotine release was much slower and primarily depended upon the permeability of the dialysis membrane. Although total nicotine was lowest for Skoal Bandit Classic, little difference was seen in nicotine release rates among the brands tested. When smokeless tobacco was placed in dialysis bags with artificial saliva outside, a significant difference was seen in rates of nicotine migration through the membrane. In this model, nicotine release from Copenhagen Snuff was much faster than from Skoal Bandit Classic with or without the sachet. This difference may be related to the pH of the smokeless tobacco products. PMID:9606918

  9. The metabolism of [14C]nicotine in the cat

    PubMed Central

    Turner, D. M.

    1969-01-01

    The metabolism of [2′-14C]nicotine given as an intravenous injection in small doses to anaesthetized and unanaesthetized cats has been studied. A method is described for the quantitative determination of [14C]nicotine and [14C]cotinine in tissues and body fluids. Nanogram amounts of these compounds have been detected. After a single dose of 40μg. of [14C]nicotine/kg., 55% of the injected radioactivity was excreted in the urine within 24hr., but only 1% of this radioactivity was unchanged nicotine. [14C]Nicotine is metabolized extremely rapidly, [14C]cotinine appearing in the blood within 2·5min. of intravenous injection. [14C]Nicotine accumulates rapidly in the brain and 15min. after injection 90% of the radioactivity still represents [14C]nicotine. Metabolites of [14C]nicotine have been identified in liver and urine extracts. [14C]Nicotine-1′-oxide has been detected in both liver and urine. PMID:5360723

  10. Estradiol promotes the rewarding effects of nicotine in female rats.

    PubMed

    Flores, Rodolfo J; Pipkin, Joseph A; Uribe, Kevin P; Perez, Adriana; O'Dell, Laura E

    2016-07-01

    It is presently unclear whether ovarian hormones, such as estradiol (E2), promote the rewarding effects of nicotine in females. Thus, we compared extended access to nicotine intravenous self-administration (IVSA) in intact male, intact female, and OVX female rats (Study 1) as well as OVX females that received vehicle or E2 supplementation (Study 2). The E2 supplementation procedure involved a 4-day injection regimen involving 2 days of vehicle and 2 days of E2 administration. Two doses of E2 (25 or 250μg) were assessed in separate groups of OVX females in order to examine the dose-dependent effects of this hormone on the rewarding effects of nicotine. The rats were given 23-hour access to nicotine IVSA using an escalating dose regimen (0.015, 0.03, and 0.06mg/kg/0.1mL). Each dose was self-administered for 4 days with 3 intervening days of nicotine abstinence. The results revealed that intact females displayed higher levels of nicotine intake as compared to males. Also, intact females displayed higher levels of nicotine intake versus OVX females. Lastly, our results revealed that OVX rats that received E2 supplementation displayed a dose-dependent increase in nicotine intake as compared to OVX rats that received vehicle. Together, our results suggest that the rewarding effects of nicotine are enhanced in female rats via the presence of the ovarian hormone, E2. PMID:27059334

  11. Stable isotope studies of nicotine kinetics and bioavailability

    SciTech Connect

    Benowitz, N.L.; Jacob, P. 3d.; Denaro, C.; Jenkins, R. )

    1991-03-01

    The stable isotope-labeled compound 3',3'-dideuteronicotine was used to investigate the disposition kinetics of nicotine in smokers, the systemic absorption of nicotine from cigarette smoke, and the bioavailability of nicotine ingested as oral capsules. Blood levels of labeled nicotine could be measured for 9 hours after a 30-minute intravenous infusion. Analysis of disposition kinetics in 10 healthy men revealed a multiexponential decline after the end of an infusion, with an elimination half-life averaging 203 minutes. This half-life was longer than that previously reported, indicating the presence of a shallow elimination phase. Plasma clearance averaged 14.6 ml/min/kg. The average intake of nicotine per cigarette was 2.29 mg. A cigarette smoke-monitoring system that directly measured particulate matter in smoke was evaluated in these subjects. Total particulate matter, number of puffs on the cigarette, total puff volume, and time of puffing correlated with the intake of nicotine from smoking. The oral bioavailability of nicotine averaged 44%. This bioavailability is higher than expected based on the systemic clearance of nicotine and suggests that there may be significant extrahepatic metabolism of nicotine.

  12. Sensory reinforcement-enhancing effects of nicotine via smoking.

    PubMed

    Perkins, Kenneth A; Karelitz, Joshua L

    2014-12-01

    As has been found in nicotine research on animals, research on humans has shown that acute nicotine enhances reinforcement from rewards unrelated to nicotine intake, but this effect may be specific to rewards from stimuli that are "sensory" in nature. We assessed acute effects of nicotine via smoking on responding for music or video rewards (sensory), for monetary reward (nonsensory), or for no reward (control), to gauge the generalizability of nicotine's reinforcement-enhancing effects. Using a fully within-subjects design, dependent smokers (N = 20) participated in 3 similar experimental sessions, each following overnight abstinence (verified by carbon monoxide <10 ppm) and varying only in the smoking condition. Sessions involved no smoking or smoking "denicotinized" ("denic;" 0.05 mg) or nicotine (0.6 mg) Quest brand cigarettes in controlled fashion prior to responding on a simple operant computer task for each reward separately using a progressive ratio schedule. The reinforcing effects of music and video rewards, but not money, were significantly greater due to the nicotine versus denic cigarette (i.e., nicotine per se), whereas there were no differences between denic cigarette smoking and no smoking (i.e., smoking behavior per se), except for no reward. These effects were not influenced by withdrawal relief from either cigarette. Results that generalize from an auditory to a visual reward confirm that acute nicotine intake per se enhances the reinforcing value of sensory rewards, but its effects on the value of other (perhaps nonsensory) types of rewards may be more modest. PMID:25180451

  13. CRF neurons in the ventral tegmental area control the aversive effects of nicotine withdrawal and promote escalation of nicotine intake

    PubMed Central

    Grieder, Taryn E.; Herman, Melissa A.; Contet, Candice; Tan, Laura A.; Vargas-Perez, Hector; Cohen, Ami; Chwalek, Michal; Maal-Bared, Geith; Freiling, John; Schlosburg, Joel E; Clarke, Laura; Crawford, Elena; Koebel, Pascale; Canonigo, Vez; Sanna, Pietro; Tapper, Andrew; Roberto, Marisa; Kieffer, Brigitte L.; Sawchenko, Paul E.; Koob, George F.; van der Kooy, Derek; George, Olivier

    2014-01-01

    SUMMARY Dopaminergic neurons in the ventral tegmental area (VTA) are well known for their role in mediating the positive reinforcing effects of drugs of abuse. Here, we identify in rodents and humans a population of VTA dopamine neurons co-expressing corticotropin releasing factor (CRF). We provide further evidence in rodents that chronic nicotine exposure upregulates CRF mRNA in dopaminergic neurons of the posterior VTA, activates local CRF1 receptors, and blocks nicotine-induced activation of transient GABAergic input to dopaminergic neurons. Local downregulation of CRF mRNA and specific pharmacological blockade of CRF1 receptors in the VTA reversed the effect of nicotine on GABAergic input to dopaminergic neurons, prevented the aversive effects of nicotine withdrawal, and limited the escalation of nicotine intake. These results link the brain reward and stress systems within the same brain region in signaling the negative motivational effects of nicotine withdrawal. PMID:25402857

  14. Effects of maternal nicotine on breastfeeding infants.

    PubMed

    Primo, Cândida Caniçali; Ruela, Priscilla Bôa F; Brotto, Léia Damasceno de A; Garcia, Telma Ribeiro; Lima, Eliane de Fátima

    2013-09-01

    OBJECTIVE To assess scientific evidence about the effects of maternal nicotine on infant by an integrative review. DATA SOURCES Studies published in Portuguese, English and Spanish, from 1990 to 2009, with abstracts available in the Latin American Health Sciences Literature (Lilacs) and Medical Literature Analysis and Retrieval System On-Line (Medline) databases. The descriptors were: "breastfeeding", "lactation" and "smoking". DATA SYNTHESIS The main identified effects of nicotine on infants were: changes in sleep and wakefulness patterns; reduction of iodine supply; hystopathological damage on liver and lung; intracellular oxidative damage; reduction of pancreatic ß cells; and decreased glucose tolerance. CONCLUSIONS It is recommended to inform mothers about harmful chemicals contained in cigarettes that can be secreted into breast milk. They should be strongly encouraged to stop smoking during lactation. PMID:24142324

  15. Synthesis and biodistribution of radioiodinated nicotine analogs

    SciTech Connect

    Chan, S.M.; Basmadjian, G.P.; Marten, D.F.; Sadek, S.; Magarian, R.A.; Grunder, J.R.; Ice, R.D.

    1984-01-01

    The authors reported previously on the synthesis and biodistribution of radioiodinated 5-iodonicotine. In their continuous effort to search for a potential brain as well as adrenal medulla imaging agent, the authors synthesized four radioiodinated nicotine analogs. The labeled compounds were prepared by brominating nicotinic acid, and reacting the acylated product with the appropriate amines to give the respective amides which were then reduced with diborane to the amines. I-125 labeling was done by halogen exchange. Biodistribution studies performed in female Sprague-Dawley rats showed that all these compounds were taken up rapidly by the brain and the adrenal. The highest uptake of all these compounds in both organs occurred at 2 minutes after tail vein injections. The organ:blood ratios at 2 minutes and the T/sub 1/3/ (min.) of radioactivity in these organs were compared.

  16. Nicotine addiction through a neurogenomic prism

    PubMed Central

    Caron, Lorraine; Karkazis, Katrina; Raffin, Thomas A.; Swan, Gary; Koenig, Barbara A.

    2008-01-01

    Studies are under way to examine the neurogenetic factors contributing to smoking behaviors. The combined approaches of genomics, molecular biology, neuroscience, and pharmacology are expected to fuel developments in pharmacogenetics, to create new genetic tests, and ultimately to provide the basis for innovative strategies for smoking cessation and prevention. The emergence of a neurogenomic understanding of nicotine addiction is likely to induce fundamental changes in popular, clinical, and public health views of smoking, which could significantly shape existing practices and policies to reduce tobacco use. Still a nascent area of research, nicotine addiction provides an excellent case study through which to anticipate key ethical and policy issues in both behavioral genetics and the neurogenomics of addictive behaviors. PMID:16036275

  17. Effects of maternal nicotine on breastfeeding infants

    PubMed Central

    Primo, Cândida Caniçali; Ruela, Priscilla Bôa F.; Brotto, Léia Damasceno de A.; Garcia, Telma Ribeiro; Lima, Eliane de Fátima

    2013-01-01

    OBJECTIVE To assess scientific evidence about the effects of maternal nicotine on infant by an integrative review. DATA SOURCES Studies published in Portuguese, English and Spanish, from 1990 to 2009, with abstracts available in the Latin American Health Sciences Literature (Lilacs) and Medical Literature Analysis and Retrieval System On-Line (Medline) databases. The descriptors were: "breastfeeding", "lactation" and "smoking". DATA SYNTHESIS The main identified effects of nicotine on infants were: changes in sleep and wakefulness patterns; reduction of iodine supply; hystopathological damage on liver and lung; intracellular oxidative damage; reduction of pancreatic ß cells; and decreased glucose tolerance. CONCLUSIONS It is recommended to inform mothers about harmful chemicals contained in cigarettes that can be secreted into breast milk. They should be strongly encouraged to stop smoking during lactation. PMID:24142324

  18. Effects of a Selective Cannabinoid CB2 Agonist and Antagonist on Intravenous Nicotine Self Administration and Reinstatement of Nicotine Seeking

    PubMed Central

    Gamaleddin, Islam; Zvonok, Alexander; Makriyannis, Alexandros; Goldberg, Steven R.; Le Foll, Bernard

    2012-01-01

    Over the last decade there have been significant advances in the discovery and understanding of the cannabinoid system along with the development of pharmacologic tools that modulate its function. Characterization of the crosstalk between nicotine addiction and the cannabinoid system may have significant implications on our understanding of the neurobiological mechanisms underlying nicotine dependence. Two types of cannabinoid receptors (CB1 and CB2) have been identified. CB1 receptors are expressed in the brain and modulate drug taking and drug seeking for various drugs of abuse, including nicotine. CB2 receptors have been recently identified in the brain and have been proposed to play a functional role in mental disorders and drug addiction. Our objective was to explore the role of CB2 receptors on intravenous nicotine self administration under two schedules of reinforcement (fixed and progressive ratio) and on nicotine seeking induced by nicotine priming or by nicotine associated cues. For this, we evaluated the effects of various doses of the selective CB2 antagonist AM630 (1.25 to 5 mg/kg) and CB2 agonist AM1241 (1 to 10 mg/kg) on these behavioral responses in rats. Different groups of male Long Evans rats were trained to lever press for nicotine at a unit dose of 30 µg/kg/infusion. Subsequently, animals were randomized using a Latin-square design and injected with either AM1241 or AM630 using a counterbalanced within subject design. Administration of the CB2 ligands did not affect either nicotine-taking nicotine-seeking behavior. Our results do not support the involvement of CB2 receptors in nicotine-taking or nicotine-seeking behavior. PMID:22291896

  19. Nicotinic receptor blockade decreases fos immunoreactivity within orexin/hypocretin-expressing neurons of nicotine-exposed rats.

    PubMed

    Simmons, Steven J; Gentile, Taylor A; Mo, Lili; Tran, Fionya H; Ma, Sisi; Muschamp, John W

    2016-11-01

    Tobacco smoking is the leading cause of preventable death in the United States. Nicotine is the principal psychoactive ingredient in tobacco that causes addiction. The structures governing nicotine addiction, including those underlying withdrawal, are still being explored. Nicotine withdrawal is characterized by negative affective and cognitive symptoms that enhance relapse susceptibility, and suppressed dopaminergic transmission from ventral tegmental area (VTA) to target structures underlies behavioral symptoms of nicotine withdrawal. Agonist and partial agonist therapies help 1 in 4 treatment-seeking smokers at one-year post-cessation, and new targets are needed to more effectively aid smokers attempting to quit. Hypothalamic orexin/hypocretin neurons send excitatory projections to dopamine (DA)-producing neurons of VTA and modulate mesoaccumbal DA release. The effects of nicotinic receptor blockade, which is commonly used to precipitate withdrawal, on orexin neurons remain poorly investigated and present an attractive target for intervention. The present study sought to investigate the effects of nicotinic receptor blockade on hypothalamic orexin neurons using mecamylamine to precipitate withdrawal in rats. Separate groups of rats were treated with either chronic nicotine or saline for 7-days at which point effects of mecamylamine or saline on somatic signs and anxiety-like behavior were assessed. Finally, tissue from rats was harvested for immunofluorescent analysis of Fos within orexin neurons. Results demonstrate that nicotinic receptor blockade leads to reduced orexin cell activity, as indicated by lowered Fos-immunoreactivity, and suggest that this underlying cellular activity may be associated with symptoms of nicotine withdrawal as effects were most prominently observed in rats given chronic nicotine. We conclude from this study that orexin transmission becomes suppressed in rats upon nicotinic receptor blockade, and that behavioral symptoms associated

  20. Nicotine response genetics in the zebrafish

    PubMed Central

    Petzold, Andrew M.; Balciunas, Darius; Sivasubbu, Sridhar; Clark, Karl J.; Bedell, Victoria M.; Westcot, Stephanie E.; Myers, Shelly R.; Moulder, Gary L.; Thomas, Mark J.; Ekker, Stephen C.

    2009-01-01

    Tobacco use is predicted to result in over 1 billion deaths worldwide by the end of the 21st century. How genetic variation contributes to the observed differential predisposition in the human population to drug dependence is unknown. The zebrafish (Danio rerio) is an emerging vertebrate model system for understanding the genetics of behavior. We developed a nicotine behavioral assay in zebrafish and applied it in a forward genetic screen using gene-breaking transposon mutagenesis. We used this method to molecularly characterize bdav/cct8 and hbog/gabbr1.2 as mutations with altered nicotine response. Each have a single human ortholog, identifying two points for potential scientific, diagnostic, and drug development for nicotine biology and cessation therapeutics. We show this insertional method generates mutant alleles that are reversible through Cre-mediated recombination, representing a conditional mutation system for the zebrafish. The combination of this reporter-tagged insertional mutagen approach and zebrafish provides a powerful platform for a rich array of questions amenable to genetic-based scientific inquiry, including the basis of behavior, epigenetics, plasticity, stress, memory, and learning. PMID:19858493

  1. Nicotine improves the functional activity of late endothelial progenitor cells via nicotinic acetylcholine receptors.

    PubMed

    Yu, Min; Liu, Qian; Sun, Jing; Yi, Kaihong; Wu, Libiao; Tan, Xuerui

    2011-08-01

    The aim of this study is to investigate whether nicotinic acetylcholine receptors (nAChRs) are involved in the modulation of functional activity of late endothelial progenitor cells (EPCs) induced by nicotine. Total mononuclear cells (MNCs) were isolated from human umbilical cord blood by Ficoll density gradient centrifugation, and then the cells were plated on fibronectin-coated culture plates. Late EPCs were positive for 1,1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine-labeled acetylated low-density lipoprotein (DiI-acLDL) uptake and fluorescein-isothiocyanate-conjugated Ulex europaeus agglutinin lectin (UEA-1) binding. Expression of von Willbrand factor (vWF), kinase insert domain receptor (KDR), and α7 nAChR was detected by indirect immunofluorescence staining. Late EPCs of 3-5 passages were treated for 32 h with either vehicle or nicotine with or without pre-incubation of nAChR antagonism, mecamylamine, or α-bungarotoxin. The viability, migration, and in vitro vasculogenesis activity of late EPCs were assayed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, modified Boyden chamber assay, and in vitro angiogenesis assay, respectively. Late EPCs adhesion assay was performed by replating cells on fibronectin-coated plates, and then adherent cells were counted. Incubation with 10 nmol/L nicotine enhanced viable, migratory, adhesive, and in vitro vasculogenesis capacity of late EPCs. The effect of nicotine on late EPCs can be attenuated by mecamylamine or α-bungarotoxin. In conclusion, nicotine improves the functional activity of late EPCs via nAChRs. PMID:21774635

  2. Impairment of contextual fear extinction by chronic nicotine and withdrawal from chronic nicotine is associated with hippocampal nAChR upregulation.

    PubMed

    Kutlu, Munir Gunes; Oliver, Chicora; Huang, Peng; Liu-Chen, Lee-Yuan; Gould, Thomas J

    2016-10-01

    Chronic nicotine and withdrawal from chronic nicotine have been shown to be major modulators of fear learning behavior. Moreover, recent studies from our laboratory have shown that acute nicotine impaired fear extinction and safety learning in mice. However, the effects of chronic nicotine and withdrawal on fear extinction are unknown. Therefore, the current experiments were conducted to investigate the effects of chronic nicotine as well as withdrawal from chronic nicotine on contextual fear extinction in mice. C57BL6/J mice were given contextual fear conditioning training and retention testing during chronic nicotine administration. Mice then received contextual fear extinction either during chronic nicotine or during withdrawal from chronic nicotine. Our results showed that contextual fear extinction was impaired both during chronic nicotine administration and subsequent withdrawal. However, it was also observed that the effects of prior chronic nicotine disappeared after 72 h in withdrawal, a timeline that closely matches with the timing of the chronic nicotine-induced upregulation of hippocampal nicotinic acetylcholine receptor (nAChR) density. Additional experiments found that 4 days, but not 1 day, of continuous nicotine administration upregulated hippocampal nAChRs and impaired contextual fear extinction. These effects disappeared following 72 h withdrawal. Overall, these experiments provide a potential link between nicotine-induced upregulation of hippocampal nAChRs and fear extinction deficits observed in patients with anxiety disorders, which may lead to advancements in the pharmacological treatment methods for this disorder. PMID:27378334

  3. Role of β4* Nicotinic Acetylcholine Receptors in the Habenulo-Interpeduncular Pathway in Nicotine Reinforcement in Mice.

    PubMed

    Harrington, Lauriane; Viñals, Xavier; Herrera-Solís, Andrea; Flores, Africa; Morel, Carole; Tolu, Stefania; Faure, Philippe; Maldonado, Rafael; Maskos, Uwe; Robledo, Patricia

    2016-06-01

    Nicotine exerts its psychopharmacological effects by activating the nicotinic acetylcholine receptor (nAChR), composed of alpha and/or beta subunits, giving rise to a diverse population of receptors with a distinct pharmacology. β4-containing (β4*) nAChRs are located almost exclusively in the habenulo-interpeduncular pathway. We examined the role of β4* nAChRs in the medial habenula (MHb) and the interpeduncular nucleus (IPN) in nicotine reinforcement using behavioral, electrophysiological, and molecular techniques in transgenic mice. Nicotine intravenous self-administration (IVSA) was lower in constitutive β4 knockout (KO) mice at all doses tested (7.5, 15, 30, and 60 μg/kg/infusion) compared with wild-type (WT) mice. In vivo microdialysis showed that β4KO mice have higher extracellular dopamine (DA) levels in the nucleus accumbens than in WT mice, and exhibit a differential sensitivity to nicotine-induced DA outflow. Furthermore, electrophysiological recordings in the ventral tegmental area (VTA) demonstrated that DA neurons of β4KO mice are more sensitive to lower doses of nicotine than that of WT mice. Re-expression of β4* nAChRs in IPN neurons fully restored nicotine IVSA, and attenuated the increased sensitivity of VTA DA neurons to nicotine. These findings suggest that β4* nAChRs in the IPN have a role in maintaining nicotine IVSA. PMID:26585290

  4. Synthesis of Na2Mg3X2 (X = Sn, Pb) and Na4Mg4Sn3 and their crystal structures and thermoelectric properties

    NASA Astrophysics Data System (ADS)

    Yamada, Takahiro; Ishiyama, Ryo; Yamane, Hisanori

    2015-07-01

    Novel ternary stannides and a plumbide, Na2Mg3X2 (X = Sn, Pb) and Na4Mg4Sn3, were synthesized by heating the corresponding elements. The crystal structures were determined by single-crystal X-ray diffraction analysis, and the electrical conductivities and Seebeck coefficients were measured. The crystal structures of Na2Mg3X2 [orthorhombic, a = 7.3066(9) Å, b = 14.4559(13) Å, c = 6.6433(7) Å for X = Sn, a = 7.4272(11), b = 14.770(3), c = 6.6852(11) Å for X = Pb] are based on the Mg5Ga2-type structure (space group Ibam, Z = 4). Na4Mg4Sn3 crystallizes in an orthorhombic cell [a = 6.879(3) Å, b = 7.154(2) Å, c = 22.285(7) Å, space group Fmmm, Z = 4] with layers of disordered Na atom arrangement with defects. The electrical conductivities measured for the polycrystalline sintered samples of Na2Mg3Sn2, Na4Mg4Sn3, and Na2Mg3Pb2 were 1.9 × 105 S m-1 at 300 K, 1.6 × 105 S m-1 at 307 K and 3.3 × 105 S m-1 at 300 K, respectively. The Seebeck coefficients (S) of Na2Mg3Sn2, Na4Mg4Sn3, and Na2Mg3Pb2 were +47 to +72, +29 to +67, and +10 to +24 µV K-1, respectively, and increased with increasing temperature of 300-600 K.

  5. Environmental fate and effects of nicotine released during cigarette production.

    PubMed

    Seckar, Joel A; Stavanja, Mari S; Harp, Paul R; Yi, Yongsheng; Garner, Charles D; Doi, Jon

    2008-07-01

    A variety of test methods were used to study the gradation, bioaccumulation, and toxicity of nicotine. Studies included determination of the octanol-water partition coefficient, conversion to CO2 in soil and activated sludge, and evaluation of the effects on microbiological and algal inhibition as well as plant germination and root elongation. The partitioning of nicotine between octanol and water indicated that nicotine will not bioaccumulate regardless of the pH of the medium. The aqueous and soil-based biodegradation studies indicated that nicotine is readily biodegradable in both types of media. The microbiological inhibition and aquatic and terrestrial toxicity tests indicated that nicotine has low toxicity. The U.S. Environmental Protection Agency Persistence, Bioaccumulation, and Toxicity Profiler model, based on the structure of nicotine and the predictive rates of hydroxyl radical and ozone reactions, estimated an atmospheric half-life of less than 5.0 h. Using this value in the Canadian Environmental Modeling Center level III model, the half-life of nicotine was estimated as 3.0 d in water and 0.5 d in soil. This model also estimated nicotine discharge into the environment; nicotine would be expected to be found predominantly in water (93%), followed by soil (4%), air (3%), and sediment (0.4%). Using the estimated nicotine concentrations in water, soil, and sediment and the proper median effective concentrations derived from the algal growth, biomass inhibition, and buttercrunch lettuce (Lactuca sativa) seed germination and root elongation studies, hazard quotients of between 10(-7) and 10(-8) were calculated, providing further support for the conclusion that the potential for nicotine toxicity to aquatic and terrestrial species in the environment is extremely low. PMID:18399728

  6. Low-temperature sintering and compatibility with silver electrode of Ba{sub 4}MgTi{sub 11}O{sub 27} microwave dielectric ceramic

    SciTech Connect

    Chen, Xiuli; Zhou, Huanfu; Fang, Liang; Liu, Laijun; Li, Changda; Guo, Ruli; Wang, Hong

    2010-10-15

    Ba{sub 4}MgTi{sub 11}O{sub 27} microwave dielectric ceramic was investigated using X-ray diffraction, scanning electron microscopy and dielectric measurement. The pure Ba{sub 4}MgTi{sub 11}O{sub 27} ceramic shows a high sintering temperature ({approx}1275 {sup o}C) and good microwave dielectric properties as Q x f of 19,630 GHz, {epsilon}{sub r} of 36.1, {tau}{sub f} of 14.6 ppm/{sup o}C. It was found that the addition of BaCu(B{sub 2}O{sub 5}) (BCB) can effectively lower the sintering temperature from 1275 to 925 {sup o}C, and does not induce much degradation of the microwave dielectric properties. The BCB-doped Ba{sub 4}MgTi{sub 11}O{sub 27} ceramics can be compatible with Ag electrode, which makes it a promising ceramic for LTCC technology application.

  7. High capacity multicomponent hydrogen storage materials: Investigation of the effect of stoichiometry and decomposition conditions on the cycling behaviour of LiBH 4-MgH 2

    NASA Astrophysics Data System (ADS)

    Walker, Gavin S.; Grant, David M.; Price, Tobias C.; Yu, Xuebin; Legrand, Vincent

    LiBH 4-MgH 2 is an attractive reversible hydrogen storage system, it combines two high capacity hydrides (18.3 and 7.6 wt.%, respectively) and the concerted dehydrogenation reaction has a smaller enthalpy change than either species on its own. The latter effect leads to a destabilisation of the hydrided products and results in a lowering of the dehydrogenation temperature. In situ neutron diffraction experiments have been undertaken to characterise the mechanism of decomposition of the LiBD 4-MgD 2 system, with an emphasis on investigating the synergistic effects of the components during cycling under various conditions. This study compares the effect of stoichiometry of the multicomponent system on the cycling mechanism. Results show that LiBD 4-MgD 2 in a 2:1 molar ratio can be reversibly dehydrogenated under low pressures of hydrogen or under vacuum, contrary to earlier reports in the literature, although the reaction was only partially reversed for the 2:1 mixture decomposed under vacuum. This work shows that the reaction pathway was affected by dehydrogenation conditions, but the stoichiometry of the multicomponent system played a minor role.

  8. Hypocretins regulate the anxiogenic-like effects of nicotine and induce reinstatement of nicotine-seeking behavior

    PubMed Central

    Plaza-Zabala, Ainhoa; Martín-García, Elena; de Lecea, Luis; Maldonado, Rafael; Berrendero, Fernando

    2010-01-01

    Emerging evidence suggests that the hypocretinergic system is involved in addictive behavior. In this study, we investigated the role of these hypothalamic neuropeptides in anxiety-like responses of nicotine and stress-induced reinstatement of nicotine-seeking behavior. Acute nicotine (0.8 mg/kg, sc) induced anxiogenic-like effects in the elevated plus-maze and activated the paraventricular nucleus of the hypothalamus (PVN) as revealed by c-Fos expression. Pretreatment with the hypocretin receptor 1 (Hcrtr-1) antagonist SB334867 or prepro-hypocretin gene deletion blocked both nicotine effects. In the PVN, SB334867 also prevented the activation of corticotrophin releasing factor (CRF) and arginine-vasopressin (AVP) neurons, which expressed Hcrtr-1. In addition, an increase of the percentage of c-Fos positive hypocretin cells in the perifornical and dorsomedial hypothalamic (PFA/DMH) areas was found after nicotine (0.8 mg/kg, sc) administration. Intracerebroventricular (icv) infusion of hypocretin-1 (Hcrt-1) (0.75 nmol/1 μl) or footshock stress reinstated a previously extinguished nicotine-seeking behavior. The effects of Hcrt-1 were blocked by SB334867, but not by the CRF1 receptor antagonist antalarmin. Moreover, SB334867 did not block CRF-dependent footshock-induced reinstatement of nicotine-seeking while antalarmin was effective in preventing this nicotine motivational response. Therefore, the Hcrt system interacts with CRF and AVP neurons in the PVN and modulates the anxiogenic-like effects of nicotine whereas Hcrt and CRF play a different role in the reinstatement of nicotine-seeking. Indeed, Hcrt-1 reinstates nicotine-seeking through a mechanism independent of CRF activation whereas CRF mediates the reinstatement induced by stress. PMID:20147556

  9. L-theanine inhibits nicotine-induced dependence via regulation of the nicotine acetylcholine receptor-dopamine reward pathway.

    PubMed

    Di, Xiaojing; Yan, Jingqi; Zhao, Yan; Chang, Yanzhong; Zhao, Baolu

    2012-12-01

    In this study, the inhibitory effect of L-theanine, an amino acid derivative of tea, on the rewarding effects of nicotine and its underlying mechanisms of action were studied. We found that L-theanine inhibited the rewarding effects of nicotine in a conditioned place preference (CPP) model of the mouse and reduced the excitatory status induced by nicotine in SH-SY5Y cells to the same extent as the nicotine receptor inhibitor dihydro-beta-erythroidine (DHβE). Further studies using high performance liquid chromatography, western blotting and immunofluorescence staining analyses showed that L-theanine significantly inhibited nicotine-induced tyrosine hydroxylase (TH) expression and dopamine production in the midbrain of mice. L-theanine treatment also reduced the upregulation of the α(4), β(2) and α(7) nicotine acetylcholine receptor (nAChR) subunits induced by nicotine in mouse brain regions that related to the dopamine reward pathway, thus decreasing the number of cells that could react to nicotine. In addition, L-theanine treatment inhibited nicotine-induced c-Fos expression in the reward circuit related areas of the mouse brain. Knockdown of c-Fos by siRNA inhibited the excitatory status of cells but not the upregulation of TH induced by nicotine in SH-SY5Y cells. Overall, the present study showed that L-theanine reduced the nicotine-induced reward effects via inhibition of the nAChR-dopamine reward pathway. These results may offer new therapeutic strategies for treatment of tobacco addiction. PMID:23233221

  10. Sex differences in nicotine self-administration in rats during progressive unit dose reduction: Implications for nicotine regulation policy

    PubMed Central

    Grebenstein, Patricia; Burroughs, Danielle; Zhang, Yan; LeSage, Mark G.

    2013-01-01

    Reducing the nicotine content in tobacco products is being considered by the FDA as a policy to reduce the addictiveness of tobacco products. Understanding individual differences in response to nicotine reduction will be critical to developing safe and effective policy. Animal and human research demonstrating sex differences in the reinforcing effects of nicotine suggests that males and females may respond differently to nicotine-reduction policies. However, no studies have directly examined sex differences in the effects of nicotine unit-dose reduction on nicotine self-administration (NSA) in animals. The purpose of the present study was to examine this issue in a rodent self-administration model. Male and female rats were trained to self-administer nicotine (0.06 mg/kg) under an FR 3 schedule during daily 23 h sessions. Rats were then exposed to saline extinction and reacquisition of NSA, followed by weekly reductions in the unit dose (0.03 to 0.00025 mg/kg) until extinction levels of responding were achieved. Males and females were compared with respect to baseline levels of intake, resistance to extinction, degree of compensatory increases in responding during dose reduction, and the threshold reinforcing unit dose of nicotine. Exponential demand-curve analysis was also conducted to compare the sensitivity of males and females to increases in the unit price (FR/unit dose) of nicotine (i.e., elasticity of demand or reinforcing efficacy). Females exhibited significantly higher baseline intake and less compensation than males. However, there were no sex differences in the reinforcement threshold or elasticity of demand. Dose–response relationships were very well described by the exponential demand function (r2 values > 0.96 for individual subjects). These findings suggest that females may exhibit less compensatory smoking in response to nicotine reduction policies, even though their nicotine reinforcement threshold and elasticity of demand may not differ from

  11. Sex differences in nicotine self-administration in rats during progressive unit dose reduction: implications for nicotine regulation policy.

    PubMed

    Grebenstein, Patricia; Burroughs, Danielle; Zhang, Yan; LeSage, Mark G

    2013-12-01

    Reducing the nicotine content in tobacco products is being considered by the FDA as a policy to reduce the addictiveness of tobacco products. Understanding individual differences in response to nicotine reduction will be critical to developing safe and effective policy. Animal and human research demonstrating sex differences in the reinforcing effects of nicotine suggests that males and females may respond differently to nicotine-reduction policies. However, no studies have directly examined sex differences in the effects of nicotine unit-dose reduction on nicotine self-administration (NSA) in animals. The purpose of the present study was to examine this issue in a rodent self-administration model. Male and female rats were trained to self-administer nicotine (0.06mg/kg) under an FR 3 schedule during daily 23h sessions. Rats were then exposed to saline extinction and reacquisition of NSA, followed by weekly reductions in the unit dose (0.03 to 0.00025mg/kg) until extinction levels of responding were achieved. Males and females were compared with respect to baseline levels of intake, resistance to extinction, degree of compensatory increases in responding during dose reduction, and the threshold reinforcing unit dose of nicotine. Exponential demand-curve analysis was also conducted to compare the sensitivity of males and females to increases in the unit price (FR/unit dose) of nicotine (i.e., elasticity of demand or reinforcing efficacy). Females exhibited significantly higher baseline intake and less compensation than males. However, there were no sex differences in the reinforcement threshold or elasticity of demand. Dose-response relationships were very well described by the exponential demand function (r(2) values>0.96 for individual subjects). These findings suggest that females may exhibit less compensatory smoking in response to nicotine reduction policies, even though their nicotine reinforcement threshold and elasticity of demand may not differ from males

  12. N(N)-nicotinic blockade as an acute human model of autonomic failure

    NASA Technical Reports Server (NTRS)

    Jordan, J.; Shannon, J. R.; Black, B. K.; Lance, R. H.; Squillante, M. D.; Costa, F.; Robertson, D.

    1998-01-01

    Pure autonomic failure has been conceptualized as deficient sympathetic and parasympathetic innervation. Several recent observations in chronic autonomic failure, however, cannot be explained simply by loss of autonomic innervation, at least according to our current understanding. To simulate acute autonomic failure, we blocked N(N)-nicotinic receptors with intravenous trimethaphan (6+/-0.4 mg/min) in 7 healthy subjects (4 men, 3 women, aged 32+/-3 years, 68+/-4 kg, 171+/-5 cm). N(N)-Nicotinic receptor blockade resulted in near-complete interruption of sympathetic and parasympathetic efferents as indicated by a battery of autonomic function tests. With trimethaphan, small postural changes from the horizontal were associated with significant blood pressure changes without compensatory changes in heart rate. Gastrointestinal motility, pupillary function, saliva production, and tearing were profoundly suppressed with trimethaphan. Plasma norepinephrine level decreased from 1.1+/-0.12 nmol/L (180+/-20 pg/mL) at baseline to 0.23+/-0.05 nmol/L (39+/-8 pg/mL) with trimethaphan (P<.001). There was a more than 16-fold increase in plasma vasopressin (P<.01) and no change in plasma renin activity. We conclude that blockade of N(N)-cholinergic receptors is useful to simulate the hemodynamic alterations of acute autonomic failure in humans. The loss of function with acute N(N)-cholinergic blockade is more complete than in most cases of chronic autonomic failure. This difference may be exploited to elucidate the contributions of acute denervation and chronic adaptation to the pathophysiology of autonomic failure. N(N)-Cholinergic blockade may also be applied to study human cardiovascular physiology and pharmacology in the absence of confounding baroreflexes.

  13. Nicotine-induced impulsive action: sensitization and attenuation by mecamylamine

    PubMed Central

    Kirshenbaum, Ari P.; Jackson, Eric R.; Brown, Seth J.; Fuchs, Jason R.; Miltner, Betsie C.; Doughty, Adam H.

    2011-01-01

    A conjunctive variable-interval differential-reinforcement-of-low-rate (VI-DRL, n= 18) responding schedule and a stop-signal task (n= 18) were used to evaluate the disinhibiting effects of nicotine on response withholding in rats. Sucrose solution was used to reinforce responding, and after a stable baseline was achieved under saline-administration conditions, 0.3 mg/kg nicotine was delivered before each session. Experiment 1 showed that repeated, but not the initial, administration of nicotine decreased performance on both tasks, and the effect of sensitization followed a similar timeline; 10 consecutive doses resulted in poorer proportion-correct VI-DRL trials and percent correct stop trials than the initial dose of nicotine. Furthermore, sensitization to 0.3 mg/kg nicotine decreased performance regardless of whether a spaced or consecutive-dosing regimen was followed. Experiment 2 was designed to test whether mecamylamine hydrochloride (0.1–1.0 mg/kg) could attenuate the effects of repeated 0.3 mg/kg nicotine administration, and the degree to which mecamylamine attenuation of the effect of nicotine to produce impulsive action was relative to dose. Results from experiment 2 showed that response disinhibition, as evaluated using the VI-DRL and stop-signal tasks, is related in a systematic manner to nicotinic-acetylcholine receptor activation. PMID:21448062

  14. Noribogaine reduces nicotine self-administration in rats

    PubMed Central

    Chang, Qing; Hanania, Taleen; Mash, Deborah C

    2015-01-01

    Noribogaine, a polypharmacological drug with activities at opioid receptors, ionotropic nicotinic receptors, and serotonin reuptake transporters, has been investigated for treatment of substance abuse-related disorders. Smoking cessation has major benefits for both individuals and society, therefore the aim of this study was to evaluate the potential of noribogaine for use as a treatment for nicotine dependence. Adult male Sprague-Dawley rats were trained to self-administer nicotine intravenous. After initial food pellet training, followed by 26 sessions of nicotine self-administration training, the rats were administered noribogaine (12.5, 25 or 50 mg/kg orally), noribogaine vehicle, varenicline or saline using a within-subject design with a Latin square test schedule. Noribogaine dose-dependently decreased nicotine self-administration by up to 64% of saline-treated rats’ levels and was equi-effective to 1.7 mg/kg intraperitoneal varenicline. Noribogaine was less efficient at reducing food pellets self-administration than at nicotine self-administration, inhibiting the nondrug reinforcing effects of palatable pellets by 23% at the highest dose. These results suggest that noribogaine dose-dependently attenuates drug-taking behavior for nicotine, attenuates the reinforcing effects of nicotine and is comparable to varenicline power in that regard. The findings from the present study hold promise for a new therapy to aid smoking cessation. PMID:25995321

  15. [New prospects of nicotine dependence treatment--vaccines].

    PubMed

    Goniewicz, Maciej Lukasz; Koszowski, Bartosz; Czogała, Jan; Zymełka, Anna

    2006-01-01

    Smoking is considered to be one of the main threats to health in many societies around the world. Despite carrying out numerous large-scale campaigns promoting a healthy life-style and stimulant avoidance, nicotine dependence still concerns a huge group of people. What is more, almost half of the population is exposed to passive contact with tobacco smoke. At present, there is a whole range of pharmaceutical and non-pharmaceutical means of fighting nicotine dependence. The dramatic development of medical sciences in recent years, especially of the fields connected with biotechnology, resulted in working out of a new method of nicotinism treatment--antinicotinic vaccines. The starting point for working out of such drugs was the mechanism of nicotine action on central nervous system. The idea behind the vaccine is to prevent nicotine from passing through the blood-brain barrier. Nicotine molecules, due to their size and lipophilic character, can easily enter the brain. The mechanism of the antinicotinic vaccine's action consists in producing specific antibodies, which combined with nicotine in the bloodstream are to create immune complexes big enough not to enter the brain. Currently, clinical trails of three vaccines are being carried out: TA-NIC (Xenova Group, UK), NicVAX (NABI Biopharmaceuticals, USA), CYT002-NicQb (Cytos Biotechnology, Switzerland). The results indicate that this form of treatment is interesting when it comes to its effectiveness and in the future may become a routine method of nicotine dependence treatment. PMID:17288232

  16. Effects of Nicotine Fading and Relapse Prevention on Smoking Cessation.

    ERIC Educational Resources Information Center

    Brown, Richard A.; And Others

    1984-01-01

    Conducted a pilot study which combined nicotine-fading and relapse prevention with smokers (N=30) and compared this program to conditions where subjects (N=46) received nicotine-fading or relapse prevention only. Results showed no difference among groups in abstinence or rate at any follow-up point. (LLL)

  17. A Critical Evaluation of Nicotine Replacement Therapy for Teenage Smokers.

    ERIC Educational Resources Information Center

    Patten, Christi A.

    2000-01-01

    Evaluates the appropriateness and feasibility of nicotine replacement therapy (NRT) in teenage smokers. Available forms of NRT, theoretical rationale and efficacy of NRT, ethical considerations, and the feasibility of NRT in teenage smokers are addressed. Several characteristics similar to adult nicotine dependent smokers have been found in teen…

  18. Educating Smokers about Their Cigarettes and Nicotine Medications

    ERIC Educational Resources Information Center

    Bansal-Travers, Maansi; Cummings, K. Michael; Hyland, Andrew; Brown, Anthony; Celestino, Paula

    2010-01-01

    The objective of this study was to test the efficacy of specially designed educational materials to correct misperceptions held by smokers about nicotine, nicotine medications, low tar cigarettes, filters and product ingredients. To accomplish this, 682 New York State Smokers' Quitline callers were randomized to one of two groups: control group…

  19. Noribogaine reduces nicotine self-administration in rats.

    PubMed

    Chang, Qing; Hanania, Taleen; Mash, Deborah C; Maillet, Emeline L

    2015-06-01

    Noribogaine, a polypharmacological drug with activities at opioid receptors, ionotropic nicotinic receptors, and serotonin reuptake transporters, has been investigated for treatment of substance abuse-related disorders. Smoking cessation has major benefits for both individuals and society, therefore the aim of this study was to evaluate the potential of noribogaine for use as a treatment for nicotine dependence. Adult male Sprague-Dawley rats were trained to self-administer nicotine intravenous. After initial food pellet training, followed by 26 sessions of nicotine self-administration training, the rats were administered noribogaine (12.5, 25 or 50 mg/kg orally), noribogaine vehicle, varenicline or saline using a within-subject design with a Latin square test schedule. Noribogaine dose-dependently decreased nicotine self-administration by up to 64% of saline-treated rats' levels and was equi-effective to 1.7 mg/kg intraperitoneal varenicline. Noribogaine was less efficient at reducing food pellets self-administration than at nicotine self-administration, inhibiting the nondrug reinforcing effects of palatable pellets by 23% at the highest dose. These results suggest that noribogaine dose-dependently attenuates drug-taking behavior for nicotine, attenuates the reinforcing effects of nicotine and is comparable to varenicline power in that regard. The findings from the present study hold promise for a new therapy to aid smoking cessation. PMID:25995321

  20. Biocidal action of chlorhexidine is annulled by nicotinic acid.

    PubMed Central

    Baker, H; Frank, O; DeAngelis, B; Baker, E R

    1994-01-01

    An analytical system comprising a bacterium and a protozoan was used to pinpoint the metabolic lesion whereby chlorhexidine (CLX) produced cell death. Nicotinic acid but not nicotinamide annulled the biocidal action of CLX. The results suggest that CLX may not permit bioconversion of nicotinamide to nicotinic acid to annul the growth inhibition induced by CLX. PMID:7840588

  1. How Prepared Are Psychiatry Residents for Treating Nicotine Dependence?

    ERIC Educational Resources Information Center

    Prochaska, Judith J.; Fromont, Sebastien C.; Hall, Sharon M.

    2005-01-01

    Objective: Nicotine dependence is the most prevalent substance abuse disorder among adult psychiatric patients and a leading cause of death and disability. The authors examined the extent to which psychiatry residents are prepared to treat nicotine dependence in clinical practice. Methods: Residents from five psychiatry residency programs in…

  2. Facial EMG as an Index of Affective Response to Nicotine

    PubMed Central

    Robinson, Jason D.; Cinciripini, Paul M.; Carter, Brian L.; Lam, Cho Y.; Wetter, David W.

    2016-01-01

    Negative affect reduction has been postulated to be a key feature of cigarette smoking. In the present study, facial electromyography (EMG), heart rate (HR), and skin conductance (SCR) were used to evaluate the affective significance of acute nicotine administration and overnight withdrawal. Smokers (n=115) attended four 90-min laboratory assessment sessions scheduled approximately three days apart. The four sessions provided a complete crossing of two pre-laboratory deprivation conditions (12-hour deprived vs. nondeprived) with two drug conditions (nicotine vs. placebo nasal spray). During each session, smokers viewed affective slides while facial EMG, HR, and SCR were recorded. Results indicated that for women, nicotine nasal spray resulted in lower corrugator EMG activity during both smoking-deprived and nondeprived sessions, compared to placebo. However, nondeprived women also showed an increase in zygomaticus EMG when given nicotine compared to placebo spray, while smoking-deprived women demonstrated a decrease in the zygomaticus response to nicotine compared to placebo. With men, nicotine also appeared to lower corrugator during deprivation, but not nondeprivation, compared to placebo spray, though the contrast only approached significance. With zygomaticus EMG, nicotine spray decreased men’s zygomaticus responding during nondeprivation but not during deprivation, compared to placebo spray. The HR results reflected the stimulatory properties of the drug rather than nicotine’s affective properties, while SCR was unresponsive to our experimental manipulations. The corrugator EMG results support negative reinforcement models of smoking that postulate that acute nicotine use reduces withdrawal-driven negative affect. PMID:17696686

  3. A pilot study on nicotine residues in houses of electronic cigarette (e-cigarette) users, tobacco smokers, and non-users of nicotine-containing products

    PubMed Central

    Bush, Derek; Goniewicz, Maciej L.

    2015-01-01

    Background Nicotine deposited on the surfaces has been shown to react with airborne chemicals leading to formation of carcinogens and contributing to thirdhand exposure. While prior studies revealed nicotine residues in tobacco smokers' homes, none have examined the nicotine residue in electronic cigarette (e-cigarette) users' homes. Methods We measured nicotine on the surfaces in households of 8 e-cigarette users, 6 cigarette smokers, and 8 non-users of nicotine-containing products in Western New York, USA. Three surface wipe samples were taken from the floor, wall and window. Nicotine was extracted from the wipes and analyzed using gas chromatography. Results Half of the e-cigarette users' homes had detectable levels of nicotine on surfaces whereas nicotine was found in all of the tobacco cigarette smokers' homes. Trace amounts of nicotine were also detected in half of the homes of non-users of nicotine-containing products. Nicotine levels in e-cigarette users homes was significantly lower than that found in cigarette smokers homes (average concentration 7.7±17.2 vs. 1,303±2,676 μg/m2; p<0.05). There was no significant difference in the amount of nicotine in homes of e-cigarette users and non-users (p>0.05). Conclusions Nicotine is a common contaminant found on indoor surfaces. Using e-cigarettes indoors leads to significantly less thirdhand exposure to nicotine compared to smoking tobacco cigarettes. PMID:25869751

  4. Discriminating nicotine and non-nicotine containing e-liquids using infrared spectroscopy.

    PubMed

    Deconinck, E; Bothy, J L; Barhdadi, S; Courselle, P

    2016-02-20

    In a few countries, including Belgium, nicotine-containing e-cigarettes and e-liquids are considered medicines, and therefore cannot freely be sold, but should be distributed in a pharmacy. The fact that in the neighbouring countries these products are freely available, poses a problem for custom personnel, the more the nicotine content of the products is not always labelled, especially when they are bought through internet. Therefore there is a need for easy-to-use equipment and methods to perform a first on site screening of intercepted samples, both for border control as to check label compliance of the sample. The use of attenuated total reflectance-infrared spectroscopy (ATR-IR) and near infrared spectroscopy (NIR), combined with chemometrics was evaluated for the discrimination between nicotine containing and non-nicotine containing samples. It could be concluded that both ATR-IR and NIR could be used for the discrimination when combined with the appropriate chemometric techniques. The presented techniques do not need sample preparation and result in models with a minimum of false negative samples. If a large enough training set can be established the interpretation can be fully automated, making the presented approach suitable for on-site screening of e-liquid samples. PMID:26771132

  5. Historical and Current Perspective on Tobacco use and Nicotine Addiction

    PubMed Central

    Dani, John A.; Balfour, David J.K.

    2011-01-01

    Although the addictive influence of tobacco was recognized very early, the modern concepts of nicotine addiction have relied on knowledge of cholinergic neurotransmission and nicotinic acetylcholine receptors (nAChRs). The discovery of the “receptive substance” by Langley, that would turn out to be nAChRs, and “Vagusstoff” (acetylcholine) by Loewi, coincided with an exciting time when the concept of chemical synaptic transmission was being formulated. More recently, the application of more powerful techniques and the study of animal models that replicate key features of nicotine dependence have led to important advancements in our understanding of molecular, cellular, and systems mechanisms of nicotine addiction. In this Review, we present a historical perspective and overview of the research that has led to our present understanding of nicotine addiction. PMID:21696833

  6. Biosynthesis of trigonelline from nicotinate mononucleotide in mungbean seedlings.

    PubMed

    Zheng, Xin-Qiang; Matsui, Ayu; Ashihara, Hiroshi

    2008-01-01

    To determine the biosynthetic pathway to trigonelline, the metabolism of [carboxyl-(14)C]nicotinate mononucleotide (NaMN) and [carboxyl-(14)C]nicotinate riboside (NaR) in protein extracts and tissues of embryonic axes from germinating mungbeans (Phaseolus aureus) was investigated. In crude cell-free protein extracts, in the presence of S-adenosyl-L-methionine, radioactivity from [(14)C]NaMN was incorporated into NaR, nicotinate and trigonelline. Activities of NaMN nucleotidase, NaR nucleosidase and trigonelline synthase were also observed in the extracts. Exogenously supplied [(14)C]NaR, taken up by embryonic axes segments, was readily converted to nicotinate and trigonelline. It is concluded that the NaMN-->NaR-->nicotinate-->trigonelline pathway is operative in the embryonic axes of mungbean seedlings. This result suggests that trigonelline is synthesised not only from NAD but also via the de novo biosynthetic pathway of pyridine nucleotides. PMID:17888466

  7. Chronic injections of saline produce subsensitivity to nicotine.

    PubMed

    Flemmer, D D; Dilsaver, S C

    1989-10-01

    The routine handling of rats and the injection of saline is a stressor. The authors report that chronic twice daily injections of normal saline (1 ml/kg IP) for 14 days produced subsensitivity to the hypothermic effects of nicotine (1 ml/kg IP). The weekly injection of nicotine (1 mg/kg IP) does not produce this effect. The investigators propose that their findings reflect the effect of chronic stress on a nicotinic mechanism. Lithium, desipramine, fluoxetine, and amitriptyline also alter the thermic response to systemically injected nicotine. A nicotinic mechanism(s) may be involved in the neurobiology of chronic stress, actions of antidepressants, and conceivably the pathophysiology of depression. PMID:2622980

  8. Nicotinic cholinergic receptors in rat brain. Annual report No. 2

    SciTech Connect

    Kellar, K.J.

    1985-05-13

    We have conducted experiments to determine if 3H acetylcholine (3Hach) nicotinic recognition sites are located presynaptically on catecholamine and/or serotonin axons. Lesions of these axons by intraventricular injections of neurotoxins resulted in marked decreases in 3Hach binding sites in the striatum and hypothalamus, but not in the cortex or thalamus. These results indicate that 3Hach nicotinic binding sites are located on catecholamine and serotonin axons in specific areas of the brain. In other experiments, we determined that repeated administration of nicotine results in enhanced behavioral responses to a subsequent injection of nicotine, and that there appears to be a correlation between the enhanced response to nicotine and increased 3Hach binding sites in cerebral cortex.

  9. Recent developments in the synthesis of nicotinic acetylcholine receptor ligands.

    PubMed

    Breining, Scott R

    2004-01-01

    The extraordinary pharmacology of nicotine and epibatidine have indicated the potential for nicotinic acetylcholine receptor (nAChR) ligands to serve as a new therapeutic class for a host of CNS disorders. Many such ligands are natural products, or analogs thereof, which represent a significant challenge to the synthetic chemist. Synthesis of such molecules often serves as a showcase to demonstrate the potential of newly developed methodology. This synthetic challenge coupled with the promise of pharmacological activity in compounds possessing the nicotinic pharmacophore has stimulated a great deal of synthetic activity over the last five years. The present report provides an overview of novel synthetic methodology occurring during this period directed toward the synthesis of compounds with presumed affinity for the neuronal nAChR. Syntheses chosen for review here represent the major efforts toward molecules such as epibatidine analogs, anatoxin-a, nicotine and related alkaloids, conformationally constrained nicotine derivatives, cytisine and methyllycaconitine (MLA). PMID:14965298

  10. Knowledge and Perceptions about Nicotine, Nicotine Replacement Therapies and Electronic Cigarettes among Healthcare Professionals in Greece.

    PubMed

    Moysidou, Anastasia; Farsalinos, Konstantinos E; Voudris, Vassilis; Merakou, Kyriakoula; Kourea, Kallirrhoe; Barbouni, Anastasia

    2016-01-01

    Introduction. The purpose of this study was to evaluate the knowledge and perceptions of Greek healthcare professionals about nicotine, nicotine replacement therapies and electronic cigarettes. Methods. An online survey was performed, in which physicians and nurses working in private and public healthcare sectors in Athens-Greece were asked to participate through email invitations. A knowledge score was calculated by scoring the correct answers to specific questions with 1 point. Results. A total of 262 healthcare professionals were included to the analysis. Most had daily contact with smokers in their working environment. About half of them considered that nicotine has an extremely or very important contribution to smoking-related disease. More than 30% considered nicotine replacement therapies equally or more addictive than smoking, 76.7% overestimated their smoking cessation efficacy and only 21.0% would recommend them as long-term smoking substitutes. For electronic cigarettes, 45.0% considered them equally or more addictive than smoking and 24.4% equally or more harmful than tobacco cigarettes. Additionally, 35.5% thought they involve combustion while the majority responded that nicotine in electronic cigarettes is synthetically produced. Only 14.5% knew about the pending European regulation, but 33.2% have recommended them to smokers in the past. Still, more than 40% would not recommend electronic cigarettes to smokers unwilling or unable to quit smoking with currently approved medications. Cardiologists and respiratory physicians, who are responsible for smoking cessation therapy in Greece, were even more reluctant to recommend electronic cigarettes to this subpopulation of smokers compared to all other participants. The knowledge score of the whole study sample was 7.7 (SD: 2.4) out of a maximum score of 16. Higher score was associated with specific physician specialties. Conclusions. Greek healthcare professionals appear to overestimate the adverse effects

  11. Roles of nicotinic acetylcholine receptor β subunits in function of human α4-containing nicotinic receptors

    PubMed Central

    Wu, Jie; Liu, Qiang; Yu, Kewei; Hu, Jun; Kuo, Yen-Ping; Segerberg, Marsha; St John, Paul A; Lukas, Ronald J

    2006-01-01

    Naturally expressed nicotinic acetylcholine receptors (nAChR) containing α4 subunits (α4*-nAChR) in combination with β2 subunits (α4β2-nAChR) are among the most abundant, high-affinity nicotine binding sites in the mammalian brain. β4 subunits are also richly expressed and colocalize with α4 subunits in several brain regions implicated in behavioural responses to nicotine and nicotine dependence. Thus, α4β4-nAChR also may exist and play important functional roles. In this study, properties were determined of human α4β2- and α4β4-nAChR heterologously expressed de novo in human SH-EP1 epithelial cells. Whole-cell currents mediated via human α4β4-nAChR have ∼4-fold higher amplitude than those mediated via human α4β2-nAChR and exhibit much slower acute desensitization and functional rundown. Nicotinic agonists induce peak whole-cell current responses typically with higher functional potency at α4β4-nAChR than at α4β2-nAChR. Cytisine and lobeline serve as full agonists at α4β4-nAChR but are only partial agonists at α4β2-nAChR. However, nicotinic antagonists, except hexamethonium, have comparable affinities for functional α4β2- and α4β4-nAChR. Whole-cell current responses show stronger inward rectification for α4β2-nAChR than for α4β4-nAChR at a positive holding potential. Collectively, these findings demonstrate that human nAChR β2 or β4 subunits can combine with α4 subunits to generate two forms of α4*-nAChR with distinctive physiological and pharmacological features. Diversity in α4*-nAChR is of potential relevance to nervous system function, disease, and nicotine dependence. PMID:16825297

  12. Knowledge and Perceptions about Nicotine, Nicotine Replacement Therapies and Electronic Cigarettes among Healthcare Professionals in Greece

    PubMed Central

    Moysidou, Anastasia; Farsalinos, Konstantinos E.; Voudris, Vassilis; Merakou, Kyriakoula; Kourea, Kallirrhoe; Barbouni, Anastasia

    2016-01-01

    Introduction. The purpose of this study was to evaluate the knowledge and perceptions of Greek healthcare professionals about nicotine, nicotine replacement therapies and electronic cigarettes. Methods. An online survey was performed, in which physicians and nurses working in private and public healthcare sectors in Athens-Greece were asked to participate through email invitations. A knowledge score was calculated by scoring the correct answers to specific questions with 1 point. Results. A total of 262 healthcare professionals were included to the analysis. Most had daily contact with smokers in their working environment. About half of them considered that nicotine has an extremely or very important contribution to smoking-related disease. More than 30% considered nicotine replacement therapies equally or more addictive than smoking, 76.7% overestimated their smoking cessation efficacy and only 21.0% would recommend them as long-term smoking substitutes. For electronic cigarettes, 45.0% considered them equally or more addictive than smoking and 24.4% equally or more harmful than tobacco cigarettes. Additionally, 35.5% thought they involve combustion while the majority responded that nicotine in electronic cigarettes is synthetically produced. Only 14.5% knew about the pending European regulation, but 33.2% have recommended them to smokers in the past. Still, more than 40% would not recommend electronic cigarettes to smokers unwilling or unable to quit smoking with currently approved medications. Cardiologists and respiratory physicians, who are responsible for smoking cessation therapy in Greece, were even more reluctant to recommend electronic cigarettes to this subpopulation of smokers compared to all other participants. The knowledge score of the whole study sample was 7.7 (SD: 2.4) out of a maximum score of 16. Higher score was associated with specific physician specialties. Conclusions. Greek healthcare professionals appear to overestimate the adverse effects

  13. Electronic Cigarettes Are a Source of Thirdhand Exposure to Nicotine

    PubMed Central

    Lee, Lily

    2015-01-01

    Introduction: Substances remaining on the surfaces in areas where people have smoked contribute to thirdhand exposure. Nicotine from tobacco smoke has been shown to react with oxidizing chemicals in the air to form secondary pollutants, such as carcinogenic nitrosamines. While prev ious studies have demonstrated thirdhand exposure to nicotine from tobacco smoke, none have investigated whether nicotine from electronic cigarettes (e-cigarettes) can also be deposited on various surfaces. Methods: Three brands of e-cigarettes were refilled with varying nicotine concentrations. We released 100 puffs from each product directly into an exposure chamber. Surface wipe samples were taken from 5 indoor 100cm2 surfaces (window, walls, floor, wood, and metal) pre- and post-release of vapors. Nicotine was extracted from the wipes and was analyzed using gas chromatography. Results: Three of the 4 experiments showed significant increases in the amount of nicotine on all five surfaces. The floor and glass windows had the greatest increases in nicotine, on average by a factor of 47 and 6, respectively (p < .05). The average amount of nicotine deposited on a floor during each experiment was 205 μg/m2 and varied from limit of quantitation to 550 μg/m2. Conclusions: This study indicates that there is a risk for thirdhand exposure to nicotine from e-cigarettes. Thirdhand exposure levels differ depending on the surface and the e-cigarette brand. Future research should explore the potential risks of thirdhand exposure to carcinogens formed from the nicotine that is released from e-cigarettes. PMID:25173774

  14. Incorporation of Nicotine into Silicone Coatings for Marine Applications

    NASA Astrophysics Data System (ADS)

    Jaramillo, Sandy Tuyet

    PDMS-based marine coatings presently used are limited by their inability to mitigate microfouling which limits their application to high speed vessels. PDMS coatings are favored when viable, due to their foul release properties of macrofouling organisms. Natural products have been investigated for antifouling properties for potential use in these marine antifouling coatings but few have incorporated natural products into coatings or coating systems. The purpose of the research was to establish the corrosion inhibiting properties of nicotine and to incorporate nicotine, a biodegradable and readily available natural product, into a PDMS coating to demonstrate the use of a natural product in a coating for marine applications. The corrosion inhibiting properties of nicotine was examined using potentiodynamic polarization scans, material characterization techniques such as scanning electron microscopy, energy dispersive spectroscopy and X-ray diffraction, quartz crystal microbalance and electrochemical impedance spectroscopy. Nicotine was determined to be an anodic corrosion inhibitor for mild steel immersed in simulated seawater with the ability to precipitate a protective calcium carbonate film. Electrochemical impedance spectroscopy was used to evaluate the performance of the developed nicotine incorporated coatings on mild steel immersed in simulated seawater over 21 days of immersion. The coatings with 2 wt.% of nicotine incorporated in the coating with a ratio of 1:30 of additional platinum catalyst to nicotine exhibited the best performance for intact coatings. This coating had the most favorable balance of the amount of nicotine and platinum catalyst of all the coatings evaluated. Overall, all nicotine incorporated coatings had a performance improvement when compared to the control PDMS coating. Of the nicotine incorporated coatings that were tested with an artificial pin-hole defect, the 2PDMS coating also exhibited the best performance with significant

  15. Nicotine Reduces Antipsychotic-Induced Orofacial Dyskinesia in Rats

    PubMed Central

    Bordia, Tanuja; McIntosh, J. Michael

    2012-01-01

    Antipsychotics are an important class of drugs for the management of schizophrenia and other psychotic disorders. They act by blocking dopamine receptors; however, because these receptors are present throughout the brain, prolonged antipsychotic use also leads to serious side effects. These include tardive dyskinesia, repetitive abnormal involuntary movements of the face and limbs for which there is little treatment. In this study, we investigated whether nicotine administration could reduce tardive dyskinesia because nicotine attenuates other drug-induced abnormal movements. We used a well established model of tardive dyskinesia in which rats injected with the commonly used antipsychotic haloperidol develop vacuous chewing movements (VCMs) that resemble human orofacial dyskinesias. Rats were first administered nicotine (minipump; 2 mg/kg per day). Two weeks later, they were given haloperidol (1 mg/kg s.c.) once daily. Nicotine treatment reduced haloperidol-induced VCMs by ∼20% after 5 weeks, with a significant ∼60% decline after 13 weeks. There was no worsening of haloperidol-induced catalepsy. To understand the molecular basis for this improvement, we measured the striatal dopamine transporter and nicotinic acetylcholine receptors (nAChRs). Both haloperidol and nicotine treatment decreased the transporter and α6β2* nAChRs (the asterisk indicates the possible presence of other nicotinic subunits in the receptor complex) when given alone, with no further decline with combined drug treatment. By contrast, nicotine alone increased, while haloperidol reduced α4β2* nAChRs in both vehicle and haloperidol-treated rats. These data suggest that molecular mechanisms other than those directly linked to the transporter and nAChRs underlie the nicotine-mediated improvement in haloperidol-induced VCMs in rats. The present results are the first to suggest that nicotine may be useful for improving the tardive dyskinesia associated with antipsychotic use. PMID:22144565

  16. New trends in the treatment of nicotine addiction.

    PubMed

    Sliwińska-Mossoń, Mariola; Zieleń, Iwona; Milnerowicz, Halina

    2014-01-01

    The aim of this study was to discuss the therapeutic substances used to treat nicotine addiction, not registered in Poland. This paper presents the results of the latest clinical trials and the possibility of their use in the treatment of nicotine addiction. The first two discussed drugs clonidine and nortriptyline are recommended by clinical practice guidelines AHRQ (Agency for Healthcare Research and Quality) as the substance of the second line in the fight against addiction. Nortriptyline belongs to tricyclic antidepressants. Its mechanism of action is the inhibition of the reuptake of norepinephrine. It is suggested as the antagonist of activity of nicotinic receptors. The results confirm its efficacy in the treatment of nicotine addiction, but many side effects limit its use. Clonidine acts presumably by inhibition of sympathetic hyperactivity characteristic of symptoms associated with nicotine rehab. The remaining compounds under discussion, such as: venlafaxine, fluoxetine, moclobemide and rimonabant, are not registered in any country with an indication to use in the treatment of nicotine addiction, however, due to the mechanism in which they act, the possibility of their use in the treatment of this disease is considered. The possibility of using anxiolytics such as: buspirone, diazepam, meprobamate and beta-blockers: metoprolol and oxprenolol is also considered in order to treat the anxiety appearing as one of the symptoms of abstinence. An interesting proposal to combat nicotine addiction are vaccines--NicVAX, CYT002-NicQb and TA-NIC. Currently, they are in clinical phase I and II of their development. Their operation would be based on the induction of specific antibodies that bind nicotine in the plasma, thus prevent it reaching the nicotinic receptors. Preliminary results confirm the possible positive effects in the prevention and treatment of nicotine addiction. PMID:25272878

  17. The effects of nicotine and non-nicotine smoking factors on working memory and associated brain function.

    PubMed

    McClernon, Francis Joseph; Froeliger, Brett; Rose, Jed E; Kozink, Rachel V; Addicott, Merideth A; Sweitzer, Maggie M; Westman, Eric C; Van Wert, Dana M

    2016-07-01

    Smoking abstinence impairs executive function, which may promote continued smoking behavior and relapse. The differential influence of nicotine and non-nicotine (i.e. sensory, motor) smoking factors and related neural substrates is not known. In a fully factorial, within-subjects design, 33 smokers underwent fMRI scanning following 24 hours of wearing a nicotine or placebo patch while smoking very low nicotine content cigarettes or remaining abstinent from smoking. During scanning, blood oxygenation level-dependent (BOLD) signal was acquired while participants performed a verbal N-back task. Following 24-hour placebo (versus nicotine) administration, accuracy on the N-back task was significantly worse and task-related BOLD signal lower in dorsomedial frontal cortex. These effects were observed irrespective of smoking. Our data provide novel evidence that abstinence-induced deficits in working memory and changes in underlying brain function are due in large part to abstinence from nicotine compared with non-nicotine factors. This work has implications both for designing interventions that target abstinence-induced cognitive deficits and for nicotine-reduction policy. PMID:25904425

  18. COMPARISON OF NICOTINIC ANTAGONISTS IN BLOCKING THE EFFECT OF ANATOXIN-A AND NICOTINE ON THE MOTOR ACTIVITY OF RATS.

    EPA Science Inventory

    Anatoxin-a is a potent nicotinic agonist produced by many species and genera of cyanobacteria. Previous research showed that both anatoxin-a and nicotine produce dose-related decreases in the motor activity of rats. The two toxins differed, however, in their effects with weekly a...

  19. Crystal structure of human nicotinic acid phosphoribosyltransferase.

    PubMed

    Marletta, Ada Serena; Massarotti, Alberto; Orsomando, Giuseppe; Magni, Giulio; Rizzi, Menico; Garavaglia, Silvia

    2015-01-01

    Nicotinic acid phosphoribosyltransferase (EC 2.4.2.11) (NaPRTase) is the rate-limiting enzyme in the three-step Preiss-Handler pathway for the biosynthesis of NAD. The enzyme catalyzes the conversion of nicotinic acid (Na) and 5-phosphoribosyl-1-pyrophosphate (PRPP) to nicotinic acid mononucleotide (NaMN) and pyrophosphate (PPi). Several studies have underlined the importance of NaPRTase for NAD homeostasis in mammals, but no crystallographic data are available for this enzyme from higher eukaryotes. Here, we report the crystal structure of human NaPRTase that was solved by molecular replacement at a resolution of 2.9 Å in its ligand-free form. Our structural data allow the assignment of human NaPRTase to the type II phosphoribosyltransferase subfamily and reveal that the enzyme consists of two domains and functions as a dimer with the active site located at the interface of the monomers. The substrate-binding mode was analyzed by molecular docking simulation and provides hints into the catalytic mechanism. Moreover, structural comparison of human NaPRTase with the other two human type II phosphoribosyltransferases involved in NAD biosynthesis, quinolinate phosphoribosyltransferase and nicotinamide phosphoribosyltransferase, reveals that while the three enzymes share a conserved overall structure, a few distinctive structural traits can be identified. In particular, we show that NaPRTase lacks a tunnel that, in nicotinamide phosphoribosiltransferase, represents the binding site of its potent and selective inhibitor FK866, currently used in clinical trials as an antitumoral agent. PMID:26042198

  20. Crystal structure of human nicotinic acid phosphoribosyltransferase

    PubMed Central

    Marletta, Ada Serena; Massarotti, Alberto; Orsomando, Giuseppe; Magni, Giulio; Rizzi, Menico; Garavaglia, Silvia

    2015-01-01

    Nicotinic acid phosphoribosyltransferase (EC 2.4.2.11) (NaPRTase) is the rate-limiting enzyme in the three-step Preiss–Handler pathway for the biosynthesis of NAD. The enzyme catalyzes the conversion of nicotinic acid (Na) and 5-phosphoribosyl-1-pyrophosphate (PRPP) to nicotinic acid mononucleotide (NaMN) and pyrophosphate (PPi). Several studies have underlined the importance of NaPRTase for NAD homeostasis in mammals, but no crystallographic data are available for this enzyme from higher eukaryotes. Here, we report the crystal structure of human NaPRTase that was solved by molecular replacement at a resolution of 2.9 Å in its ligand-free form. Our structural data allow the assignment of human NaPRTase to the type II phosphoribosyltransferase subfamily and reveal that the enzyme consists of two domains and functions as a dimer with the active site located at the interface of the monomers. The substrate-binding mode was analyzed by molecular docking simulation and provides hints into the catalytic mechanism. Moreover, structural comparison of human NaPRTase with the other two human type II phosphoribosyltransferases involved in NAD biosynthesis, quinolinate phosphoribosyltransferase and nicotinamide phosphoribosyltransferase, reveals that while the three enzymes share a conserved overall structure, a few distinctive structural traits can be identified. In particular, we show that NaPRTase lacks a tunnel that, in nicotinamide phosphoribosiltransferase, represents the binding site of its potent and selective inhibitor FK866, currently used in clinical trials as an antitumoral agent. PMID:26042198

  1. Vulnerability to nicotine self-administration in adolescent mice correlates with age-specific expression of α4* nicotinic receptors.

    PubMed

    Renda, Anthony; Penty, Nora; Komal, Pragya; Nashmi, Raad

    2016-09-01

    The majority of smokers begin during adolescence, a developmental period with a high susceptibility to substance abuse. Adolescents are affected differently by nicotine compared to adults, with adolescents being more vulnerable to nicotine's rewarding properties. It is unknown if the age-dependent molecular composition of a younger brain contributes to a heightened susceptibility to nicotine addiction. Nicotine, the principle pharmacological component of tobacco, binds and activates nicotinic acetylcholine receptors (nAChRs) in the brain. The most prevalent is the widely expressed α4-containing (α4*) subtype which mediates reward and is strongly implicated in nicotine dependence. Exposing different age groups of mice, postnatal day (P) 44-86 days old, to a two bottle-choice oral nicotine self-administration paradigm for five days yielded age-specific consumption levels. Nicotine self-administration was elevated in the P44 group, peaked at P54-60 and was drastically lower in the P66 through P86 groups. We also quantified α4* nAChR expression via spectral confocal imaging of brain slices from α4YFP knock-in mice, in which the α4 nAChR subunit is tagged with a yellow fluorescent protein. Quantitative fluorescence revealed age-specific α4* nAChR expression in dopaminergic and GABAergic neurons of the ventral tegmental area. Receptor expression showed a strong positive correlation with daily nicotine dose, suggesting that α4* nAChR expression levels are age-specific and may contribute to the propensity to self-administer nicotine. PMID:27102349

  2. Effects of User Puff Topography, Device Voltage, and Liquid Nicotine Concentration on Electronic Cigarette Nicotine Yield: Measurements and Model Predictions

    PubMed Central

    Talih, Soha; Balhas, Zainab; Eissenberg, Thomas; Salman, Rola; Karaoghlanian, Nareg; El Hellani, Ahmad; Baalbaki, Rima; Saliba, Najat

    2015-01-01

    Introduction: Some electronic cigarette (ECIG) users attain tobacco cigarette–like plasma nicotine concentrations while others do not. Understanding the factors that influence ECIG aerosol nicotine delivery is relevant to regulation, including product labeling and abuse liability. These factors may include user puff topography, ECIG liquid composition, and ECIG design features. This study addresses how these factors can influence ECIG nicotine yield. Methods: Aerosols were machine generated with 1 type of ECIG cartridge (V4L CoolCart) using 5 distinct puff profiles representing a tobacco cigarette smoker (2-s puff duration, 33-ml/s puff velocity), a slow average ECIG user (4 s, 17 ml/s), a fast average user (4 s, 33 ml/s), a slow extreme user (8 s, 17 ml/s), and a fast extreme user (8 s, 33 ml/s). Output voltage (3.3–5.2 V or 3.0–7.5 W) and e-liquid nicotine concentration (18–36 mg/ml labeled concentration) were varied. A theoretical model was also developed to simulate the ECIG aerosol production process and to provide insight into the empirical observations. Results: Nicotine yields from 15 puffs varied by more than 50-fold across conditions. Experienced ECIG user profiles (longer puffs) resulted in higher nicotine yields relative to the tobacco smoker (shorter puffs). Puff velocity had no effect on nicotine yield. Higher nicotine concentration and higher voltages resulted in higher nicotine yields. These results were predicted well by the theoretical model (R 2 = 0.99). Conclusions: Depending on puff conditions and product features, 15 puffs from an ECIG can provide far less or far more nicotine than a single tobacco cigarette. ECIG emissions can be predicted using physical principles, with knowledge of puff topography and a few ECIG device design parameters. PMID:25187061

  3. Functional Upregulation of α4* Nicotinic Acetylcholine Receptors in VTA GABAergic Neurons Increases Sensitivity to Nicotine Reward

    PubMed Central

    Ngolab, Jennifer; Liu, Liwang; Zhao-Shea, Rubing; Gao, Guangping; Gardner, Paul D.

    2015-01-01

    Chronic nicotine exposure increases sensitivity to nicotine reward during a withdrawal period, which may facilitate relapse in abstinent smokers, yet the molecular neuroadaptation(s) that contribute to this phenomenon are unknown. Interestingly, chronic nicotine use induces functional upregulation of nicotinic acetylcholine receptors (nAChRs) in the mesocorticolimbic reward pathway potentially linking upregulation to increased drug sensitivity. In the ventral tegmental area (VTA), functional upregulation of nAChRs containing the α4 subunit (α4* nAChRs) is restricted to GABAergic neurons. To test the hypothesis that increased functional expression of α4* nAChRs in these neurons modulates nicotine reward behaviors, we engineered a Cre recombinase-dependent gene expression system to selectively express α4 nAChR subunits harboring a “gain-of-function” mutation [a leucine mutated to a serine residue at the 9′ position (Leu9′Ser)] in VTA GABAergic neurons of adult mice. In mice expressing Leu9′Ser α4 nAChR subunits in VTA GABAergic neurons (Gad2VTA:Leu9′Ser mice), subreward threshold doses of nicotine were sufficient to selectively activate VTA GABAergic neurons and elicit acute hypolocomotion, with subsequent nicotine exposures eliciting tolerance to this effect, compared to control animals. In the conditioned place preference procedure, nicotine was sufficient to condition a significant place preference in Gad2VTA:Leu9′Ser mice at low nicotine doses that failed to condition control animals. Together, these data indicate that functional upregulation of α4* nAChRs in VTA GABAergic neurons confers increased sensitivity to nicotine reward and points to nAChR subtypes specifically expressed in GABAergic VTA neurons as molecular targets for smoking cessation therapeutics. PMID:26041923

  4. Permissive nicotine regulation as a complement to traditional tobacco control

    PubMed Central

    Sumner, Walton

    2005-01-01

    Background Cigarette smoking takes a staggering toll on human health and attracts considerable public health attention, yet real solutions seem distant. The 2004 Family Smoking Prevention and Tobacco Control Act (US Senate bill S2461) would have given the US Food and Drug Administration limited authority to regulate cigarettes to "protect the public health." However, such legislation is unlikely to substantially reduce smoking or related deaths. Discussion The past 500 years of tobacco control efforts demonstrate that nicotine prohibition is a practical impossibility for numerous reasons, state revenue being one of the most ominous. The FDA already has regulatory authority over pharmaceutical grade nicotine products, and requires pharmacists to dispense the most addictive of these only with prescriptions. Meanwhile, every corner store can sell far more addictive and dangerous cigarettes to any adult. The FDA could immediately increase competition between cigarettes and clean nicotine products by approving available nicotine products for over-the-counter sales to adults. Similarly permissive regulation of cigarettes and addictive nicotine products will reduce tobacco use and improve smokers' health, but increase nicotine use in the population. Fortunately, restricted youth access and accurate labeling of nicotine's absolute risks will dissuade many non-smokers from experimenting with it, while accurate depiction of its risks relative to cigarette smoking will encourage many smokers to switch. The FDA could take a series of small steps that might ultimately replace a large proportion of cigarette smoking with equally addictive nicotine products, without risking serious public health setbacks. Vaccine, methadone, and injury prevention policies establish relevant public health precedents. Summary Cigarettes, or an equally addictive alternative, will be a permanent and common product in most societies. Regulations restricting only the safest addictive nicotine products

  5. Ternary LiBH4-MgH2-NaAlH4 hydride confined into nanoporous carbon host for reversible hydrogen storage

    NASA Astrophysics Data System (ADS)

    Plerdsranoy, Praphatsorn; Utke, Rapee

    2016-03-01

    Ternary hydride of LiBH4-MgH2-NaAlH4 confined into carbo n aerogel scaffold (CAS) via melt infiltration for reversible hydrogen storage is proposed. Nanoconfinement of hydrides into CAS is obtained together with surface occupation of some phases, such as Al and/or LiH. Regarding nanoconfinement, not only multiple-step decomposition of LiBH4-MgH2-NaAlH4 hydride reduces to about single step, but also reduction of dehydrogenation temperature is significantly observed, for example, ∆T up to 70 °C regarding last dehydrogenation step. Moreover, decomposition of NaBH4 in nanoconfined sample can be done at 360 °C (dehydrogenation temperature in this study), which is 115 and 180 °C lower than that of NaBH4 in milled LiBH4-MgH2-NaAlH4 and bulk NaBH4, respectively. The reaction of LiBH4+NaAlH4→LiAlH4+NaBH4 takes place during nanoconfinement and the decomposition of LiAlH4 is observed, resulting deficient hydrogen content liberated. However, hydrogen content released (1st cycle) and reproduced (2nd-4th cycles) from this ternary hydride enhances up to 11% and 22% of full hydrogen storage capacity due to nanoconfinement. After rehydrogenation (T=360 °C and P(H2)=50 bar H2 for 12 h), NaBH4, MgH2, and Li3AlH6 are reversible, whereas Li3AlH6 and NaBH4 in milled sample cannot be recovered due to deficient hydrogen pressure (T=360 °C and P(H2)=80 bar) and probably evaporation of molten sodium during dehydrogenation, respectively. The latter results in inferior hydrogen content reproduced from milled sample to nanoconfined sample.

  6. Thermodynamics and Kinetics of the Formation of Al2O3/ MgAl2O4/MgO in Al-Silica Metal Matrix Composite

    NASA Astrophysics Data System (ADS)

    Sreekumar, V. M.; Ravi, K. R.; Pillai, R. M.; Pai, B. C.; Chakraborty, M.

    2008-04-01

    The formation of Al2O3, MgAl2O4, and MgO has been widely studied in different Al base metal matrix composites, but the studies on thermodynamic aspects of the Al2O3/ MgAl2O4/MgO phase equilibria have been limited to few systems such as Al/Al2O3 and Al/SiC. The present study analyzes the Al2O3/MgAl2O4 and MgAl2O4/MgO equilibria with respect to the temperature and the Mg content in Al/SiO2 system using an extended Miedema model. There is a linear and parabolic variation in Mg with respect to the temperature for MgAl2O4/MgO and Al2O3/MgAl2O4 equilibria, respectively, and the influence of Si and Cu in the two equilibria is not appreciable. The experimental verification has been limited to MgAl2O4/MgO equilibria due to the high Mg content (≥0.5 wt pct) required for composite processing. The study has been carried out on two varieties of Al/SiO2 composites, i.e., Al/Silica gel and Al/Micro silica processed by liquid metallurgy route (stir casting route). MgO is found to be more stable compared to MgAl2O4 at Mg levels ≥5 and 1 wt pct in Al/Silica gel and Al/Micro silica composites, respectively, at 1073 K. MgO is also found to be more stable at lower Mg content (3 wt pct) in Al/Silica gel composite with decreasing particle size of silica gel from 180 micron to submicron and nanolevels. The MgO to MgAl2O4 transformation has taken place through a series of transition phases influenced by the different thermodynamic and kinetic parameters such as holding temperature, Mg concentration in the alloy, holding time, and silica particle size.

  7. A key role for the N/OFQ-NOP receptor system in modulating nicotine taking in a model of nicotine and alcohol co-administration.

    PubMed

    Cippitelli, Andrea; Schoch, Jennifer; Debevec, Ginamarie; Brunori, Gloria; Zaveri, Nurulain T; Toll, Lawrence

    2016-01-01

    Alcohol and nicotine are often co-abused. Although the N/OFQ-NOP receptor system is considered a potential target for development of drug abuse pharmacotherapies, especially for alcoholism, little is known about the role of this system in nicotine dependence. Furthermore, the effect of prior history of nicotine dependence on subsequent nicotine and alcohol taking is understudied. Using an operant co-administration paradigm, in which rats concurrently self-administer nicotine and alcohol, we found that nicotine dependent rats increased nicotine self-administration over time as compared to non-dependent animals, while patterns of alcohol lever pressing did not change between groups. Pretreatment with the potent NOP receptor agonist AT-202 (0.3-3 mg/kg) increased nicotine lever pressing of both dependent and non-dependent groups, whereas the selective antagonist SB612111 (1-10 mg/kg) elicited a clear reduction of nicotine responses, in both dependent and non-dependent rats. In parallel, AT-202 only produced minor changes on alcohol responses and SB612111 reduced alcohol taking at a dose that also reduced locomotor behavior. Results indicate that a history of nicotine dependence affects subsequent nicotine- but not alcohol-maintained responding, and that NOP receptor antagonism, rather than agonism, blocks nicotine self-administration, which strongly suggests a critical role for the endogenous N/OFQ in the modulation of nicotine reinforcement processes. PMID:27199205

  8. A key role for the N/OFQ-NOP receptor system in modulating nicotine taking in a model of nicotine and alcohol co-administration

    PubMed Central

    Cippitelli, Andrea; Schoch, Jennifer; Debevec, Ginamarie; Brunori, Gloria; Zaveri, Nurulain T.; Toll, Lawrence

    2016-01-01

    Alcohol and nicotine are often co-abused. Although the N/OFQ-NOP receptor system is considered a potential target for development of drug abuse pharmacotherapies, especially for alcoholism, little is known about the role of this system in nicotine dependence. Furthermore, the effect of prior history of nicotine dependence on subsequent nicotine and alcohol taking is understudied. Using an operant co-administration paradigm, in which rats concurrently self-administer nicotine and alcohol, we found that nicotine dependent rats increased nicotine self-administration over time as compared to non-dependent animals, while patterns of alcohol lever pressing did not change between groups. Pretreatment with the potent NOP receptor agonist AT-202 (0.3–3 mg/kg) increased nicotine lever pressing of both dependent and non-dependent groups, whereas the selective antagonist SB612111 (1–10 mg/kg) elicited a clear reduction of nicotine responses, in both dependent and non-dependent rats. In parallel, AT-202 only produced minor changes on alcohol responses and SB612111 reduced alcohol taking at a dose that also reduced locomotor behavior. Results indicate that a history of nicotine dependence affects subsequent nicotine- but not alcohol-maintained responding, and that NOP receptor antagonism, rather than agonism, blocks nicotine self-administration, which strongly suggests a critical role for the endogenous N/OFQ in the modulation of nicotine reinforcement processes. PMID:27199205

  9. Nicotine receptors mediating sensorimotor gating and its enhancement by systemic nicotine

    PubMed Central

    Pinnock, Farena; Bosch, Daniel; Brown, Tyler; Simons, Nadine; Yeomans, John R.; DeOliveira, Cleusa; Schmid, Susanne

    2015-01-01

    Prepulse inhibition (PPI) of startle occurs when intensity stimuli precede stronger startle-inducing stimuli by 10–1000 ms. PPI deficits are found in individuals with schizophrenia and other psychiatric disorders, and they correlate with other cognitive impairments. Animal research and clinical studies have demonstrated that both PPI and cognitive function can be enhanced by nicotine. PPI has been shown to be mediated, at least in part, by mesopontine cholinergic neurons that project to pontine startle neurons and activate muscarinic and potentially nicotine receptors (nAChRs). The subtypes and anatomical location of nAChRs involved in mediating and modulating PPI remain unresolved. We tested the hypothesis that nAChRs that are expressed by pontine startle neurons contribute to PPI. We also explored whether or not these pontine receptors are responsible for the nicotine enhancement of PPI. While systemic administration of nAChR antagonists had limited effects on PPI, PnC microinfusions of the non-α7nAChR preferring antagonist TMPH, but not of the α7nAChR antagonist MLA, into the PnC significantly reduced PPI. Electrophysiological recordings from startle-mediating PnC neurons confirmed that nicotine affects excitability of PnC neurons, which could be antagonized by TMPH, but not by MLA, indicating the expression of non-α7nAChR. In contrast, systemic nicotine enhancement of PPI was only reversed by systemic MLA and not by TMPH or local microinfusions of MLA into the PnC. In summary, our data indicate that non-α7nAChRs in the PnC contribute to PPI at stimulus intervals of 100 ms or less, whereas activation of α7nAChRs in other brain areas is responsible for the systemic nicotine enhancement of PPI. This is important knowledge for the correct interpretation of behavioral, preclinical, and clinical data as well as for developing drugs for the amelioration of PPI deficits and the enhancement of cognitive function. PMID:25717295

  10. Effect of nicotine on rectal mucus and mucosal eicosanoids.

    PubMed Central

    Zijlstra, F J; Srivastava, E D; Rhodes, M; van Dijk, A P; Fogg, F; Samson, H J; Copeman, M; Russell, M A; Feyerabend, C; Williams, G T

    1994-01-01

    Because ulcerative colitis is largely a disease of non-smokers and nicotine may have a beneficial effect on the disease, the effect of nicotine on rectal mucosa in rabbits was examined. Nicotine was given subcutaneously by an Alzet mini-pump in doses of 0.5, 1.25, and 2 mg/kg/day for 14 days to three groups of eight animals and compared with eight controls. Mean (SD) serum nicotine concentrations (ng/ml) were 3.5 (1.1), 8.8 (2.3), and 16.2 (5.2) respectively in the treated groups. The thickness of adherent mucus on rectal mucosa in controls (median 36 microns) was significantly reduced by low dose (22 microns, p = 0.0011), and increased by high dose nicotine (48 microns, p = 0.035). Incorporation of radioactive glucosamine into papain resistant glycoconjugates was unchanged, indicating that mucin synthesis was unaltered. Prostaglandins (PG) were reduced, in some cases significantly (6-keto PGF1 alpha, PGF2 alpha, and hydroxy-eicosatetraenoic acid), by nicotine, which showed an inverse dose dependence--with greatest inhibition in relation to the lowest dose. Nicotine, and possibly smoking, may affect colitis by an action on mucosal eicosanoids and on adherent surface mucus secretion in the rectum and large bowel. PMID:8307477

  11. Schizophrenia and the alpha7 nicotinic acetylcholine receptor.

    PubMed

    Martin, Laura F; Freedman, Robert

    2007-01-01

    In addition to the devastating symptoms of psychosis, many people with schizophrenia also suffer from cognitive impairment. These cognitive symptoms lead to marked dysfunction and can impact employability, treatment adherence, and social skills. Deficits in P50 auditory gating are associated with attentional impairment and may contribute to cognitive symptoms and perceptual disturbances. This nicotinic cholinergic-mediated inhibitory process represents a potential new target for therapeutic intervention in schizophrenia. This chapter will review evidence implicating the nicotinic cholinergic, and specifically, the alpha7 nicotinic receptor system in the pathology of schizophrenia. Impaired auditory sensory gating has been linked to the alpha7 nicotinic receptor gene on the chromosome 15q14 locus. A majority of persons with schizophrenia are heavy smokers. Although nicotine can acutely reverse diminished auditory sensory gating in people with schizophrenia, this effect is lost on a chronic basis due to receptor desensitization. The alpha7 nicotinic agonist 3-(2,4 dimethoxy)benzylidene-anabaseine (DMXBA) can also enhance auditory sensory gating in animal models. DMXBA is well tolerated in humans and a new study in persons with schizophrenia has found that DMXBA enhances both P50 auditory gating and cognition. alpha7 Nicotinic acetylcholine receptor agonists appear to be viable candidates for the treatment of cognitive disturbances in schizophrenia. PMID:17349863

  12. Menthol's potential effects on nicotine dependence: a tobacco industry perspective

    PubMed Central

    2011-01-01

    Objective To examine what the tobacco industry knows about the potential effects menthol may have on nicotine dependence. Methods A snowball strategy was used to systematically search the Legacy Tobacco Documents Library (http://legacy.library.ucsf.edu/) between 22 February and 29 April, 2010. Of the approximately 11 million documents available in the Legacy Tobacco Documents Library, the iterative searches returned tens of thousands of results. We qualitatively analysed a final collection of 309 documents relevant the effects of menthol on nicotine dependence. Results The tobacco industry knows that menthol overrides the harsh taste of tobacco and alleviates nicotine's irritating effects, synergistically interacts with nicotine, stimulates the trigeminal nerve to elicit a ‘liking’ response for a tobacco product, and makes low tar, low nicotine tobacco products more acceptable to smokers than non-mentholated low delivery products. Conclusion Menthol is not only used in cigarettes as a flavour additive; tobacco companies know that menthol also has sensory effects and interacts with nicotine to produce tobacco products that are easier to smoke, thereby making it easier to expose smokers, especially those who are new and uninitiated, to the addictive power of nicotine. PMID:21504929

  13. Nicotine dependence, abuse, and craving: dimensionality in an Israeli sample

    PubMed Central

    Shmulewitz, Dvora; Keyes, Katherine M.; Wall, Melanie M.; Aharonovich, Efrat; Aivadyan, Christina; Greenstein, Eliana; Spivak, Baruch; Weizman, Abraham; Frisch, Amos; Grant, Bridget F.; Hasin, Deborah

    2011-01-01

    Aims Evidence-based changes planned for DSM-5 substance use disorders (SUDs) include combining dependence and three of the abuse criteria into one disorder and adding a criterion indicating craving. Because DSM-IV did not include a category for nicotine abuse, little empirical support is available for aligning the nicotine use disorder criteria with the DSM-5 criteria for other SUDs. Design Latent variable analyses, likelihood ratio tests (LRT) and bootstrap tests were used to explore the unidimensionality, psychometric properties and information of the nicotine criteria. Setting, Participants A sample of household residents selected from the Israeli population register yielded 727 lifetime cigarette smokers. Measurements DSM-IV nicotine dependence criteria and proposed abuse and craving criteria, assessed with a structured interview. Findings Three abuse criteria (hazardous use, social/interpersonal problems, and neglect roles) were prevalent among smokers, formed a unidimensional latent trait with nicotine dependence criteria, were intermixed with dependence criteria across the severity spectrum, and significantly increased the diagnostic information over the dependence-only model. LRT results also supported including the abuse criteria (Χ23=259.63, p<0.0001). A craving criterion was shown to fit well with the other criteria. Conclusion Similar to findings from research on other substances, nicotine dependence, abuse, and craving criteria formed a single factor. The results support alignment of nicotine criteria with those for alcohol and drug use disorders in DSM-5. PMID:21545668

  14. Nicotine dependence and problem behaviors among urban South African adolescents.

    PubMed

    Pahl, Kerstin; Brook, David W; Morojele, Neo K; Brook, Judith S

    2010-04-01

    Tobacco use and its concomitant, nicotine dependence, are increasing in African countries and other parts of the developing world. However, little research has assessed nicotine dependence in South Africa or other parts of the African continent. Previous research has found that adolescent problem behaviors, including tobacco use, tend to cluster. This study examined the relationship between nicotine dependence and adolescent problem behaviors in an ethnically diverse sample of urban South African adolescents. A community sample (N = 731) consisting of "Black," "White," "Coloured," and "Indian" youths aged 12-17 years was drawn from the Johannesburg metropolitan area. Structured interviews were administered by trained interviewers. Nicotine dependence was assessed by the Fagerström Test of Nicotine Dependence. Logistic regression analyses showed that higher levels of nicotine dependence significantly predicted elevated levels of violent behavior, deviant behavior, marijuana and other illegal drug use, binge drinking, early sexual intercourse, multiple sexual partners, and inconsistent condom use, despite control on the adolescents' demographic characteristics, peer smoking, conflict with parents, peer deviance, and the availability of legal and illegal substances. These relationships were robust across ethnicity and gender. The findings indicate the need for policy makers and prevention and intervention programs in South Africa to consider adolescent nicotine dependence in conjunction with comorbid problem behaviors, including other substance use, sexual risk behaviors, and deviant behaviors. PMID:20099015

  15. Impact of Tobacco Smoke and Nicotine Exposure on Lung Development.

    PubMed

    Gibbs, Kevin; Collaco, Joseph M; McGrath-Morrow, Sharon A

    2016-02-01

    Tobacco smoke and nicotine exposure during prenatal and postnatal life can impair lung development, alter the immune response to viral infections, and increase the prevalence of wheezing during childhood. The following review examines recent discoveries in the fields of lung development and tobacco and nicotine exposure, emphasizing studies published within the last 5 years. In utero tobacco and nicotine exposure remains common, occurring in approximately 10% of pregnancies within the United States. Exposed neonates are at increased risk for diminished lung function, altered central and peripheral respiratory chemoreception, and increased asthma symptoms throughout childhood. Recently, genomic and epigenetic risk factors, such as alterations in DNA methylation, have been identified that may influence the risk for long-term disease. This review examines the impact of prenatal tobacco and nicotine exposure on lung development with a particular focus on nicotinic acetylcholine receptors. In addition, this review examines the role of prenatal and postnatal tobacco smoke and nicotine exposure and its association with augmenting infection risk, skewing the immune response toward a T-helper type 2 bias and increasing risk for developing an allergic phenotype and asthmalike symptoms during childhood. Finally, this review outlines the respiratory morbidities associated with childhood secondhand smoke and nicotine exposure and examines genetic and epigenetic modifiers that may influence respiratory health in infants and children exposed to in utero or postnatal tobacco smoke. PMID:26502117

  16. SENSORY REINFORCEMENT ENHANCING EFFECTS OF NICOTINE VIA SMOKING

    PubMed Central

    Perkins, Kenneth A.; Karelitz, Joshua L.

    2014-01-01

    As in animal research, acute nicotine in humans enhances reinforcement from rewards unrelated to nicotine intake, but this effect may be specific to rewards from stimuli that are “sensory” in nature. We assessed acute effects of nicotine via smoking on responding for music or video (“sensory”) rewards, for monetary (“non-sensory”) reward, or for no reward (control), to gauge the generalizability of nicotine’s reinforcement enhancing effects. Using a fully within-subjects design, dependent smokers (N=20) participated in three similar experimental sessions, each following overnight abstinence (verified by CO<10 ppm) and varying only in the smoking condition. Sessions involved no smoking or smoking denicotinized (0.05 mg) or nicotine (0.6 mg) QuestR brand cigarettes in controlled fashion prior to responding on a simple operant computer task for each reward separately, using a progressive ratio schedule. The reinforcing effects of music and video rewards, but not money, were significantly greater due to the nicotine versus denicotinized cigarette (i.e. nicotine per se), while there were no differences between the denicotinized cigarette versus no smoking (i.e. smoking behavior per se), except for no reward. These effects were not influenced by withdrawal relief from either cigarette. Results that generalize from an auditory to a visual reward confirm that acute nicotine intake per se enhances the reinforcing value of sensory rewards, but its effects on the value of other (perhaps non-sensory) types of rewards may be more modest. PMID:25180451

  17. Global actions of nicotine on the striatal microcircuit

    PubMed Central

    Plata, Víctor; Duhne, Mariana; Pérez-Ortega, Jesús; Hernández-Martinez, Ricardo; Rueda-Orozco, Pavel; Galarraga, Elvira; Drucker-Colín, René; Bargas, José

    2013-01-01

    The question to solve in the present work is: what is the predominant action induced by the activation of cholinergic-nicotinic receptors (nAChrs) in the striatal network given that nAChrs are expressed by several elements of the circuit: cortical terminals, dopamine terminals, and various striatal GABAergic interneurons. To answer this question some type of multicellular recording has to be used without losing single cell resolution. Here, we used calcium imaging and nicotine. It is known that in the presence of low micromolar N-Methyl-D-aspartate (NMDA), the striatal microcircuit exhibits neuronal activity consisting in the spontaneous synchronization of different neuron pools that interchange their activity following determined sequences. The striatal circuit also exhibits profuse spontaneous activity in pathological states (without NMDA) such as dopamine depletion. However, in this case, most pathological activity is mostly generated by the same neuron pool. Here, we show that both types of activity are inhibited during the application of nicotine. Nicotine actions were blocked by mecamylamine, a non-specific antagonist of nAChrs. Interestingly, inhibitory actions of nicotine were also blocked by the GABAA-receptor antagonist bicuculline, in which case, the actions of nicotine on the circuit became excitatory and facilitated neuronal synchronization. We conclude that the predominant action of nicotine in the striatal microcircuit is indirect, via the activation of networks of inhibitory interneurons. This action inhibits striatal pathological activity in early Parkinsonian animals almost as potently as L-DOPA. PMID:24223538

  18. Nicotine Dependence and Problem Behaviors Among Urban South African Adolescents

    PubMed Central

    Pahl, Kerstin; Brook, David W.; Morojele, Neo K.; Brook, Judith S.

    2010-01-01

    Tobacco use and its concomitant, nicotine dependence, are increasing in African countries and other parts of the developing world. However, little research has assessed nicotine dependence in South Africa or other parts of the African continent. Previous research has found that adolescent problem behaviors, including tobacco use, tend to cluster. This study examined the relationship between nicotine dependence and adolescent problem behaviors in an ethnically diverse sample of urban South African adolescents. A community sample (N = 731) consisting of “Black,” “White,” “Coloured,” and “Indian” youths aged 12–17 years was drawn from the Johannesburg metropolitan area. Structured interviews were administered by trained interviewers. Nicotine dependence was assessed by the Fagerström Test of Nicotine Dependence. Logistic regression analyses showed that higher levels of nicotine dependence significantly predicted elevated levels of violent behavior, deviant behavior, marijuana and other illegal drug use, binge drinking, early sexual intercourse, multiple sexual partners, and inconsistent condom use, despite control on the adolescents’ demographic characteristics, peer smoking, conflict with parents, peer deviance, and the availability of legal and illegal substances. These relationships were robust across ethnicity and gender. The findings indicate the need for policy makers and prevention and intervention programs in South Africa to consider adolescent nicotine dependence in conjunction with comorbid problem behaviors, including other substance use, sexual risk behaviors, and deviant behaviors. PMID:20099015

  19. Parazoanthoxanthin A blocks Torpedo nicotinic acetylcholine receptors.

    PubMed

    Rozman, Klara Bulc; Araoz, Romulo; Sepcić, Kristina; Molgo, Jordi; Suput, Dusan

    2010-09-01

    Nicotinic acetylcholine receptors are implicated in different nervous system-related disorders, and their modulation could improve existing therapy of these diseases. Parazoanthoxanthin A (ParaA) is a fluorescent pigment of the group of zoanthoxanthins. Since it is a potent acetylcholinesterase inhibitor, it may also bind to nicotinic acetylcholine receptors (nAChRs). For this reason its effect on Torpedo nAChR (alpha1(2)betagammadelta) transplanted to Xenopus laevis oocytes was evaluated, using the voltage-clamp technique. ParaA dose-dependently reduced the acetylcholine-induced currents. This effect was fully reversible only at lower concentrations. ParaA also reduced the Hill coefficient and the time to peak current, indicating a channel blocking mode of action. On the other hand, the combined effect of ParaA and d-tubocurarine (d-TC) on acetylcholine-induced currents exhibited only partial additivity, assuming a competitive mode of action of ParaA on nAChR. These results indicate a dual mode of action of ParaA on the Torpedo AChR. PMID:20230806

  20. Neurocircuitry of the nicotinic cholinergic system

    PubMed Central

    Bertrand, Daniel

    2010-01-01

    Continuing to discover how the brain works is one of the great challenges ahead of us. Although understanding the brain anatomy and its functional organization provided a first and indispensable foundation, it became clear that a static view was insufficient. To understand the complexity of neuronal communication, it is necessary to examine the chemical nature of the neurotransmission and, using the example of the acetylcholine receptors, follow the different layers of networks that can be distinguished. The natural alkaloid nicotine contained in tobacco leaves acts as an agonist with a subclass of acetylcholine receptors, and provides an interesting tool to approach brain functions. Analysis of the nicotinic acetylcholine receptors, which are ligand gated channels, revealed that these receptors are expressed at different critical locations on the neurons including the synaptic boutons, neurites, cell bodies, and even on the axons. These receptors can modulate the activity at the microcircuit synaptic level, in the cell processing of information, and, by acting on the velocity of action potential, the synchrony of communication between brain areas. These actions at multiple levels of brain organization provide an example of the complexity of brain neurocircuitry and an illustration of the relevance of this knowledge for psychiatry. PMID:21319492

  1. Eliciting nicotine craving with virtual smoking cues.

    PubMed

    Gamito, Pedro; Oliveira, Jorge; Baptista, André; Morais, Diogo; Lopes, Paulo; Rosa, Pedro; Santos, Nuno; Brito, Rodrigo

    2014-08-01

    Craving is a strong desire to consume that emerges in every case of substance addiction. Previous studies have shown that eliciting craving with an exposure cues protocol can be a useful option for the treatment of nicotine dependence. Thus, the main goal of this study was to develop a virtual platform in order to induce craving in smokers. Fifty-five undergraduate students were randomly assigned to two different virtual environments: high arousal contextual cues and low arousal contextual cues scenarios (17 smokers with low nicotine dependency were excluded). An eye-tracker system was used to evaluate attention toward these cues. Eye fixation on smoking-related cues differed between smokers and nonsmokers, indicating that smokers focused more often on smoking-related cues than nonsmokers. Self-reports of craving are in agreement with these results and suggest a significant increase in craving after exposure to smoking cues. In sum, these data support the use of virtual environments for eliciting craving. PMID:24660864

  2. Agonist and antagonist effects of nicotine on chick neuronal nicotinic receptors are defined by alpha and beta subunits.

    PubMed

    Hussy, N; Ballivet, M; Bertrand, D

    1994-09-01

    1. Functional neuronal nicotinic receptors were reconstituted in Xenopus oocytes by the nuclear injection of different combinations of chick and rat cDNAs encoding alpha and beta subunits. The pharmacology of these nicotinic receptors was investigated using two-electrode voltage clamp. 2. The sensitivity of the chick alpha 3/beta 2, alpha 3/beta 4, and alpha 4/beta 2 receptors to acetylcholine (ACh) and neuronal bungarotoxin differed markedly, indicating that both subunits contribute to the pharmacological properties of the receptors. 3. Nicotine acted as an agonist on the chick alpha 3/beta 4 and alpha 4/beta 2 receptors and rat alpha 3/beta 2 receptor. In contrast, nicotine (at concentrations > 3 microM) was only a weak partial agonist of the chick alpha 3/beta 2 receptor. Moreover, nicotine coapplied with 3 microM ACh on the chick alpha 3/beta 2 receptor acted as a potent competitive antagonist, with an IC50 of 0.43 microM. No antagonist effect of nicotine could be revealed on the other nicotinic receptors. 4. The effect of nicotine was tested on hybrid receptors obtained by coinjection of chick and rat cDNAs encoding the alpha 3 and beta 2 subunits (yielding the rat alpha 3/chick beta 2 and chick alpha 3/rat beta 2 receptors). Nicotine (10 microM) strongly inhibited both hybrid receptors. 5. Chimeric subunits were constructed by exchanging a segment located in the extracellular N-termini of chick alpha 3 and alpha 4 subunits and chick alpha 3 and rat alpha 3 subunits. These subunits were coexpressed in oocytes with chick or rat beta 2 subunits. The effect of nicotine on these receptors pointed to the importance of a 15 amino acid stretch located 3' of the first transmembrane segment in the determination of the agonist and antagonist action of nicotine. 6. Within this 15 amino acid segment, a single residue differs in chick and rat alpha 3 subunits, at position 198, within the ligand binding site of alpha subunits. Gln198 of the rat alpha 3 subunit was replaced

  3. Nicotine and Cotinine Exposure from Electronic Cigarettes: A Population Approach

    PubMed Central

    de Mendizábal, Nieves Vélez; Jones, David R.; Jahn, Andy; Bies, Robert R.; Brown, Joshua W.

    2015-01-01

    Background and Objectives Electronic cigarettes (e-cigarettes) are a recent technology that has gained rapid acceptance. Still, little is known about them in terms of safety and effectiveness. A basic question is how effectively they deliver nicotine, however the literature is surprisingly unclear on this point. Here, a population pharmacokinetic (PK) model was developed for nicotine and its major metabolite cotinine with the aim to provide a reliable framework for the simulation of nicotine and cotinine concentrations over time, based solely on inhalation airflow recordings and individual covariates (i.e. weight and breath carbon monoxide CO levels). Methods This study included 10 adults self-identified as heavy smokers (at least one pack per day). Plasma nicotine and cotinine concentrations were measured at regular 10-minute intervals for 90 minutes while human subjects inhaled nicotine vapor from a modified e-cigarette. Airflow measurements were recorded every 200 milliseconds throughout the session. A population PK model for nicotine and cotinine was developed based on previously published PK parameters and the airflow recordings. All the analyses were performed with the nonlinear mixed-effect modelling software NONMEM 7.2. Results The results show that e-cigarettes deliver nicotine effectively, although the pharmacokinetic profiles are lower than those achieved with regular cigarettes. Our PK model effectively predicts plasma nicotine and cotinine concentrations from the inhalation volume, and initial breath CO. Conclusion E-cigarettes are effective at delivering nicotine. This new PK model of e-cigarette usage might be used for pharmacodynamic analysis where the PK profiles are not available. PMID:25503588

  4. The effects of extrinsic context on nicotine discrimination.

    PubMed

    Duka, T; Seiss, E; Tasker, R

    2002-02-01

    There is evidence from memory studies that context acquired in parallel with the encoded material will facilitate retrieval. However, relatively little is known of how context affects drug discrimination behaviour in humans. The present study employs conventional drug discrimination procedures to investigate the effects of music, as an external cue, on nicotine drug discrimination. Subjects were trained to discriminate a low dose of nicotine (1 mg) from placebo while listening to two different types of music [elated (EL) and depressant (DE): thought to induce happy and sad mood respectively]. Half of the subjects received EL music with nicotine and DE with placebo and the other half vice versa. At the end of training, subjects who reached the criterion (80% of trials identified correctly) entered the generalization phase and were required to discriminate different doses of nicotine (0, 0.25, 0.5 and 1 mg) by indicating how similar each sample was to the training dose. Generalization took place in the presence of either EL or DE music. Nicotine-appropriate responding during generalization was linearly related to dose, with subjects being able to distinguish 0.5mg of nicotine from placebo. Nicotine-appropriate responding at generalization was higher when the context (type of music) was the same as the one employed during discrimination training when nicotine was administered (i.e. a context-dependent generalization effect was present). In addition, it was shown that the context-dependent effect was due to the properties of the EL music. These data provide the first evidence that extrinsic context can facilitate nicotine discrimination in humans. In addition, the findings suggest that this facilitatory effect is not a general effect but is sensitive to specific attributes of the context. PMID:11990718

  5. Serotonergic mechanism underlying tranylcypromine enhancement of nicotine self-administration

    PubMed Central

    Villégier, Anne-Sophie; Belluzzi, James D.; Leslie, Frances M.

    2010-01-01

    Although nicotine is generally considered to be the main psychoactive component of tobacco, growing evidence highlights the importance of non-nicotine compounds in smoking reinforcement. Monoamine oxidase (MAO) inhibition is a major consequence of smoking and MAO inhibitors, such as tranylcypromine, increase nicotine reinforcement. Tranylcypromine has multiple pharmacological effects, increasing monoamine release for a few hours immediately after its administration and blocking MAO activity for several days. To assess the relative role of these two actions, adult male rats were tested in consecutive daily 3-hr sessions for self-administration of nicotine (3μg/kg/inj, i.v.) either 20 hr or 1hr following administration of tranylcypromine (3 mg/kg). Both paradigms were shown to produce highly significant inhibition of MAO activity. However, whereas animals readily acquired self-administration when pretreated with tranylcypromine 1hr prior to testing, they did not with the longer pretreatment interval. Such animals did immediately acquire nicotine self-administration when the tranylcypromine pretreatment interval was switched to 1hr prior to testing on day 4, indicating that an acute effect of the MAO inhibitor was responsible for enhanced nicotine reinforcement. Several lines of evidence implicate serotonin (5-HT) as the mediator of this enhancement: (1) Tranyclypromine-enhanced nicotine reinforcement was blocked by the 5-HT2 receptor antagonists, ritanserin and ketanserin; (2) parachloroamphetamine (PCA), a 5-HT releaser, also enhanced nicotine self-administration in animals in which MAO activity was inhibited; (3) pretreatment with tranylcypromine increased PCA-induced 5-HT overflow in the nucleus accumbens. These findings suggest that MAO inhibition enhances serotonergic transmission, which serves a critical role in the reinforcing effects of nicotine. PMID:20936688

  6. Functional interaction between Lypd6 and nicotinic acetylcholine receptors.

    PubMed

    Arvaniti, Maria; Jensen, Majbrit M; Soni, Neeraj; Wang, Hong; Klein, Anders B; Thiriet, Nathalie; Pinborg, Lars H; Muldoon, Pretal P; Wienecke, Jacob; Imad Damaj, M; Kohlmeier, Kristi A; Gondré-Lewis, Marjorie C; Mikkelsen, Jens D; Thomsen, Morten S

    2016-09-01

    Nicotinic acetylcholine receptors (nAChRs) affect multiple physiological functions in the brain and their functions are modulated by regulatory proteins of the Lynx family. Here, we report for the first time a direct interaction of the Lynx protein LY6/PLAUR domain-containing 6 (Lypd6) with nAChRs in human brain extracts, identifying Lypd6 as a novel regulator of nAChR function. Using protein cross-linking and affinity purification from human temporal cortical extracts, we demonstrate that Lypd6 is a synaptically enriched membrane-bound protein that binds to multiple nAChR subtypes in the human brain. Additionally, soluble recombinant Lypd6 protein attenuates nicotine-induced hippocampal inward currents in rat brain slices and decreases nicotine-induced extracellular signal-regulated kinase phosphorylation in PC12 cells, suggesting that binding of Lypd6 is sufficient to inhibit nAChR-mediated intracellular signaling. We further show that perinatal nicotine exposure in rats (4 mg/kg/day through minipumps to dams from embryonic day 7 to post-natal day 21) significantly increases Lypd6 protein levels in the hippocampus in adulthood, which did not occur after exposure to nicotine in adulthood only. Our findings suggest that Lypd6 is a versatile inhibitor of cholinergic signaling in the brain, and that Lypd6 is dysregulated by nicotine exposure during early development. Regulatory proteins of the Lynx family modulate the function of nicotinic receptors (nAChRs). We report for the first time that the Lynx protein Lypd6 binds to nAChRs in human brain extracts, and that recombinant Lypd6 decreases nicotine-induced ERK phosphorylation and attenuates nicotine-induced hippocampal inward currents. Our findings suggest that Lypd6 is a versatile inhibitor of cholinergic signaling in the brain. PMID:27344019

  7. Inhibitory Learning is Modulated by Nicotinic Acetylcholine Receptors

    PubMed Central

    Meyer, Heidi C.; Putney, Rachel B.; Bucci, David J.

    2014-01-01

    Prior research has established that stimulating nicotinic acetylcholine receptors can facilitate learning and memory. However, most studies have focused on learning to emit a particular behavior, while little is known about the effects of nicotine on learning to withhold a behavioral response. The present study consisted of a dose response analysis of the effects of nicotine on negative occasion setting, a form of learned inhibition. In this paradigm, rats received one type of training trial in which presentation of a tone by itself was followed immediately by food reward. During the other type of trials, the tone was preceded by presentation of a light and no food was delivered after the tone. Rats gradually learned to approach the cup in anticipation of receiving food reward during presentations of the tone alone, but withheld that behavior when the tone was preceded by the light. Nicotine (0.35mg/kg) facilitated negative occasion setting by reducing the number of sessions needed to learn the discrimination between trial types and by reducing the rate of responding on non-reinforced trials. Nicotine also increased the orienting response to the light, suggesting that nicotine may have affected the ability to withhold food cup behavior on non-reinforced trials by increasing attention to the light. In contrast to the effects of nicotine, rats treated with mecamylamine (0.125, 0.5, or 2 mg/kg) needed more training sessions to discriminate between reinforced and non-reinforced trials compared to saline-treated rats. The findings indicate that nicotinic acetylcholine receptors may be active during negative occasion setting and that nicotine can potentiate learned inhibition. PMID:25445487

  8. Nicotine inhibits potassium currents in Aplysia bag cell neurons.

    PubMed

    White, Sean H; Sturgeon, Raymond M; Magoski, Neil S

    2016-06-01

    Acetylcholine and the archetypal cholinergic agonist, nicotine, are typically associated with the opening of ionotropic receptors. In the bag cell neurons, which govern the reproductive behavior of the marine snail, Aplysia californica, there are two cholinergic responses: a relatively large acetylcholine-induced current and a relatively small nicotine-induced current. Both currents are readily apparent at resting membrane potential and result from the opening of distinct ionotropic receptors. We now report a separate current response elicited by applying nicotine to cultured bag cell neurons under whole cell voltage-clamp. This current was ostensibly inward, best resolved at depolarized voltages, presented a noncooperative dose-response with a half-maximal concentration near 1.5 mM, and associated with a decrease in membrane conductance. The unique nicotine-evoked response was not altered by intracellular perfusion with the G protein blocker GDPβS or exposure to classical nicotinic antagonists but was occluded by replacing intracellular K(+) with Cs(+) Consistent with an underlying mechanism of direct inhibition of one or more K(+) channels, nicotine was found to rapidly reduce the fast-inactivating A-type K(+) current as well as both components of the delayed-rectifier K(+) current. Finally, nicotine increased bag cell neuron excitability, which manifested as reduction in spike threshold, greater action potential height and width, and markedly more spiking to continuous depolarizing current injection. In contrast to conventional transient activation of nicotinic ionotropic receptors, block of K(+) channels could represent a nonstandard means for nicotine to profoundly alter the electrical properties of neurons over prolonged periods of time. PMID:26864763

  9. Role of the D3 dopamine receptor in nicotine sensitization.

    PubMed

    Smith, Laura N; Bachus, Susan E; McDonald, Craig G; Smith, Robert F

    2015-08-01

    Adolescent cigarette use is associated with reduced quitting success and continued smoking in adulthood. Interestingly, polymorphisms of the dopamine D3 receptor (DRD3) gene have been associated with smoking behavior, and the receptor is expressed in an age- and brain region-dependent manner that suggests relevance to addiction. Here, we investigate the possible role of dopamine-related receptors, including DRD3 and an intriguing splice variant known as D3nf, in nicotine-induced sensitization. In adolescent and adult male rats, we examined (1) alterations occurring in dopamine receptor-related mRNAs (DRD1, DRD2, DRD3 and D3nf) at two time points during a sensitizing regimen of nicotine and (2) whether DRD3 antagonism either during the initial treatment (induction) or at a later challenge exposure (expression) is able to block nicotine sensitization. Nicotine-induced changes were seen for DRD3 and D3nf mRNAs in the nucleus accumbens shell early in repeated exposure in both age groups. DRD3 antagonism only blocked the induction of sensitization in adolescents and did not block the expression of sensitization in either age group. Adolescents and adults showed opposite DRD1 mRNA responses to nicotine treatment, while no age- and nicotine-related changes in DRD2 mRNA were observed. These data reveal important age-dependent regulation of DRD1- and DRD3-related mRNAs during the course of nicotine exposure. Furthermore, they highlight a requirement for DRD3 signaling in the development of adolescent nicotine sensitization, suggesting it may represent an appropriate target in the prevention of nicotine dependence initiated at this age. PMID:25907750

  10. Degradation Kinetics of Benzyl Nicotinate in Aqueous Solution

    PubMed Central

    Mbah, C. J.

    2010-01-01

    The degradation of benzyl nicotinate in aqueous solution over a pH range of 2.0-10.0 at 50±0.2° was studied. The degradation was determined by high performance liquid chromatography. The degradation was observed to follow apparent first-order rate kinetics and the rate constant for the decomposition at 25° was estimated by extrapolation. The reaction was shown to be hydroxide ion catalyzed and the Arrhenius plots showed the temperature dependence of benzyl nicotinate degradation. A significant increase in the stability of benzyl nicotinate was observed when glycerol or polyethylene glycol 400 was incorporated into the aqueous solution. PMID:20582189

  11. Information on tar and nicotine yields on cigarette packages.

    PubMed Central

    Davis, R M; Healy, P; Hawk, S A

    1990-01-01

    We examined information on tar and nicotine yields on the packages of 160 cigarette brands, 58 percent of the 275 brands for which tar and nicotine yields were listed in a recent Federal Trade Commission report. The tar yield was indicated on 14 percent, the nicotine yield was indicated on 11 percent. As tar yield increased among brands, the yield was progressively less likely to be shown on the package and was not disclosed on the package of any cigarette yielding 11 mg or more of tar. PMID:2327530

  12. Nicotinic Acetylcholine Receptor (nAChR) Dependent Chorda Tympani Taste Nerve Responses to Nicotine, Ethanol and Acetylcholine

    PubMed Central

    Ren, Zuo Jun; Mummalaneni, Shobha; Qian, Jie; Baumgarten, Clive M.; DeSimone, John A.; Lyall, Vijay

    2015-01-01

    Nicotine elicits bitter taste by activating TRPM5-dependent and TRPM5-independent but neuronal nAChR-dependent pathways. The nAChRs represent common targets at which acetylcholine, nicotine and ethanol functionally interact in the central nervous system. Here, we investigated if the nAChRs also represent a common pathway through which the bitter taste of nicotine, ethanol and acetylcholine is transduced. To this end, chorda tympani (CT) taste nerve responses were monitored in rats, wild-type mice and TRPM5 knockout (KO) mice following lingual stimulation with nicotine free base, ethanol, and acetylcholine, in the absence and presence of nAChR agonists and antagonists. The nAChR modulators: mecamylamine, dihydro-β-erythroidine, and CP-601932 (a partial agonist of the α3β4* nAChR), inhibited CT responses to nicotine, ethanol, and acetylcholine. CT responses to nicotine and ethanol were also inhibited by topical lingual application of 8-chlorophenylthio (CPT)-cAMP and loading taste cells with [Ca2+]i by topical lingual application of ionomycin + CaCl2. In contrast, CT responses to nicotine were enhanced when TRC [Ca2+]i was reduced by topical lingual application of BAPTA-AM. In patch-clamp experiments, only a subset of isolated rat fungiform taste cells exposed to nicotine responded with an increase in mecamylamine-sensitive inward currents. We conclude that nAChRs expressed in a subset of taste cells serve as common receptors for the detection of the TRPM5-independent bitter taste of nicotine, acetylcholine and ethanol. PMID:26039516

  13. Brain regions mediating α3β4 nicotinic antagonist effects of 18-MC on nicotine self-administration.

    PubMed

    Glick, Stanley D; Sell, Elizabeth M; McCallum, Sarah E; Maisonneuve, Isabelle M

    2011-11-01

    18-Methoxycoronaridine (18-MC), a putative anti-addictive agent, has been shown to decrease the self-administration of several drugs of abuse in rats. 18-MC is a potent antagonist at α3β4 nicotinic receptors. Consistent with high densities of α3β4 nicotinic receptors being located in the medial habenula and the interpeduncular nucleus, 18-MC has been shown to act in these regions to decrease both morphine and methamphetamine self-administration. The present study was conducted to determine if 18-MC's effect on nicotine self-administration is mediated by acting in these same brain regions. Because moderate densities of α3β4 receptors occur in the dorsolateral tegmentum, ventral tegmental area, and basolateral amygdala, these brain areas were also examined as potential sites of action of 18-MC. Local administration of 18-MC into either the medial habenula, the basolateral amygdala or the dorsolateral tegmentum decreased nicotine self-administration. Surprisingly, local administration of 18-MC into the interpeduncular nucleus increased nicotine self-administration while local administration of 18-MC into the ventral tegmental area had no effect on nicotine self-administration. Similar effects were produced by local administration of either mecamylamine or conotoxin AuIB. These data are consistent with the hypothesis that 18-MC decreases nicotine self-administration by indirectly modulating the dopaminergic mesolimbic pathway via blockade of α3β4 nicotinic receptors in the medial habenula, basolateral amygdala, and dorsolateral tegmentum. The data also suggest that an action of 18-MC in the interpeduncular nucleus may attenuate aversive and/or depressive effects of nicotine. PMID:21871879

  14. Nicotine carboxylate insecticide emulsions: effect of the fatty acid chain length.

    PubMed

    Casanova, Herley; Araque, Pedronel; Ortiz, Carlos

    2005-12-28

    The effect of fatty acid chain length on nicotine carboxylate insecticide emulsions has been studied in terms of particle size, interfacial tension, nicotine encapsulation on emulsion droplets, and bioactivity. The particle size of the nicotine emulsion and the interfacial tension at the nicotine carboxylate oil phase (0.03 M)--Tween 80 aqueous phase (0.001 M) were affected in a similar way by the change in the fatty acid chain length, which was correlated by the packing conformation of Tween 80 and nicotine carboxylate molecules as obtained by AM1 theoretical calculations. The amount of encapsulated nicotine inside the nicotine carboxylate emulsion droplets influenced the insecticide bioactivity of nicotine; this relationship was explained in terms of the acid value of the different fatty acids used to prepare the nicotine formulation. PMID:16366679

  15. Animal Models of Nicotine Exposure: Relevance to Second-Hand Smoking, Electronic Cigarette Use, and Compulsive Smoking

    PubMed Central

    Cohen, Ami; George, Olivier

    2013-01-01

    Much evidence indicates that individuals use tobacco primarily to experience the psychopharmacological properties of nicotine and that a large proportion of smokers eventually become dependent on nicotine. In humans, nicotine acutely produces positive reinforcing effects, including mild euphoria, whereas a nicotine abstinence syndrome with both somatic and affective components is observed after chronic nicotine exposure. Animal models of nicotine self-administration and chronic exposure to nicotine have been critical in unveiling the neurobiological substrates that mediate the acute reinforcing effects of nicotine and emergence of a withdrawal syndrome during abstinence. However, important aspects of the transition from nicotine abuse to nicotine dependence, such as the emergence of increased motivation and compulsive nicotine intake following repeated exposure to the drug, have only recently begun to be modeled in animals. Thus, the neurobiological mechanisms that are involved in these important aspects of nicotine addiction remain largely unknown. In this review, we describe the different animal models available to date and discuss recent advances in animal models of nicotine exposure and nicotine dependence. This review demonstrates that novel animal models of nicotine vapor exposure and escalation of nicotine intake provide a unique opportunity to investigate the neurobiological effects of second-hand nicotine exposure, electronic cigarette use, and the mechanisms that underlie the transition from nicotine use to compulsive nicotine intake. PMID:23761766

  16. Effects of Nicotine Deprivation on Craving Response Covariation in Smokers

    PubMed Central

    Sayette, Michael A.; Martin, Christopher S.; Hull, Jay G.; Wertz, Joan M.; Perrott, Michael A.

    2009-01-01

    Most models of craving propose that when cravings are strong, diverse responses—thought to index an underlying craving state— covary. Previous studies provided weak support for this hypothesis. The authors tested whether nicotine deprivation affects degree of covariation across multiple measures related to craving. Heavy and light smokers (N = 127) were exposed to smoking cues while either nicotine deprived or nondeprived. Measures included urge ratings, affective valence, a behavioral choice task assessing perceived reinforcement value of smoking, and smoking-related judgment tasks. Results indicated higher correlations in the nicotine-deprived than in nondeprived group. The measures principally responsible for this effect loaded onto a single common Craving factor for nicotine-deprived but not nondeprived smokers. These findings suggest that, under certain conditions, measures of craving-related processes covary. PMID:12653419

  17. Tobacco Harm Reduction and the Evolution of Nicotine Dependence

    PubMed Central

    2011-01-01

    In recent years, a renewed debate has developed around the potential for modified tobacco products to play a role in reducing tobacco-related harm. During the 1960s and 1970s medical experts recommended to smokers who could not quit that they switch to cigarettes with lower tar and nicotine content. At the time, survey data suggested that smokers who switched did not compensate for the reduction in nicotine by increasing their intake. However, public health scientists were hindered in their ability to evaluate the population impact of the reduced tar strategy by a limited understanding of nicotine addiction. Smoking dependence was seen as primarily psychological and social, rather than pharmacological or biological, until the late 1970s, when addiction researchers began to apply experimental techniques from other forms of drug abuse to study smoking behavior. This history has important lessons for current discussions about tobacco harm reduction and regulation of nicotine delivery. PMID:21330596

  18. Constant exposure to darkness produces supersensitivity to nicotine.

    PubMed

    Flemmer, D D; Dilsaver, S C

    1990-03-01

    Treatment with full-spectrum bright artificial light produces subsensitivity to the hypothermic effect of nicotine in the rat. The authors hypothesized that prolonged exposure to darkness would produce the opposite effect. The thermic responsiveness of 11 rats to nicotine (base), 0.25 mg/kg IP, was telemetrically measured at baseline, after 7 days of exposure to constant darkness, and 2, 5, and 12 days after being returned to standard vivarium conditions. Exposure to constant darkness enhanced the hypothermic response to nicotine. The sample exhibited a hyperthermic response to nicotine 2 and 5 days after being returned to the standard vivarium conditions with a 12-hour-light/12-hour-dark cycle. The magnitude of the hyperthermia observed is characteristic of the response to the injection of saline. Twelve days after return to standard vivarium conditions the thermic response of the sample was at baseline. PMID:2339143

  19. Modulation of Bordetella pertussis by nicotinic acid.

    PubMed

    McPheat, W L; Wardlaw, A C; Novotny, P

    1983-08-01

    Growth of Bordetella pertussis in a high concentration of nicotinic acid (NA) had a modulating effect on several properties and activities of the bacteria. Compared with normally grown cells, those grown in a high concentration of NA had reduced capacity for taking up both NA and nicotinamide (ND); they had reduced adenylate cyclase activity and showed loss of agglutinogen factors 2 and 3, but an increase in factor 1. By contrast, cells grown in a high concentration of ND showed only a slightly decreased capacity for uptake of ND and none of the other changes. Modulation of B. pertussis by NA varied with the strain and culture conditions and appeared to be distinct from the antigenic modulation induced by high Mg2+ in the culture medium. Evidence is presented for the association of a small proportion of the extracytoplasmic adenylate cyclase with the outer membrane of B. pertussis. PMID:6307872

  20. Modulation of Bordetella pertussis by nicotinic acid.

    PubMed Central

    McPheat, W L; Wardlaw, A C; Novotny, P

    1983-01-01

    Growth of Bordetella pertussis in a high concentration of nicotinic acid (NA) had a modulating effect on several properties and activities of the bacteria. Compared with normally grown cells, those grown in a high concentration of NA had reduced capacity for taking up both NA and nicotinamide (ND); they had reduced adenylate cyclase activity and showed loss of agglutinogen factors 2 and 3, but an increase in factor 1. By contrast, cells grown in a high concentration of ND showed only a slightly decreased capacity for uptake of ND and none of the other changes. Modulation of B. pertussis by NA varied with the strain and culture conditions and appeared to be distinct from the antigenic modulation induced by high Mg2+ in the culture medium. Evidence is presented for the association of a small proportion of the extracytoplasmic adenylate cyclase with the outer membrane of B. pertussis. PMID:6307872

  1. [Desensitization of the nicotinic acetylcholine receptor].

    PubMed

    Quiñonez, M; Rojas, L

    1994-01-01

    In biological membranes, ionic channels act speeding up ion movements. Each ionic channel is excited by a specific stimulus (i.e. electric, mechanical, chemical, etc.). Chemically activated ionic channels (CAIC), such as the nicotinic acetylcholine receptor (nAChR), suffer desensitization when the receptor site is still occupied by the agonist molecule. The desensitized CAIC is a non functional channel state regarded as a particular case of receptors rundown. CAIC desensitization only involve reduced activity and not their membrane elimination. Desensitization is important to control synaptic transmission and the development of the nervous system. In this review we discuss results related to its production, modulation and some aspects associated to models that consider it. Finally, an approach combining molecular biology and electrophysiology techniques to understand desensitization and its importance in biological systems is presented. PMID:8525756

  2. Conotoxins Targeting Nicotinic Acetylcholine Receptors: An Overview

    PubMed Central

    Lebbe, Eline K. M.; Peigneur, Steve; Wijesekara, Isuru; Tytgat, Jan

    2014-01-01

    Marine snails of the genus Conus are a large family of predatory gastropods with an unparalleled molecular diversity of pharmacologically active compounds in their venom. Cone snail venom comprises of a rich and diverse cocktail of peptide toxins which act on a wide variety of ion channels such as voltage-gated sodium- (NaV), potassium- (KV), and calcium- (CaV) channels as well as nicotinic acetylcholine receptors (nAChRs) which are classified as ligand-gated ion channels. The mode of action of several conotoxins has been the subject of investigation, while for many others this remains unknown. This review aims to give an overview of the knowledge we have today on the molecular pharmacology of conotoxins specifically interacting with nAChRs along with the structure–function relationship data. PMID:24857959

  3. Rapid Sensitization of Physiological, Neuronal, and Locomotor Effects of Nicotine: Critical Role of Peripheral Drug Actions

    PubMed Central

    Lenoir, Magalie; Tang, Jeremy S.; Woods, Amina S.

    2013-01-01

    Repeated exposure to nicotine and other psychostimulant drugs produces persistent increases in their psychomotor and physiological effects (sensitization), a phenomenon related to the drugs' reinforcing properties and abuse potential. Here we examined the role of peripheral actions of nicotine in nicotine-induced sensitization of centrally mediated physiological parameters (brain, muscle, and skin temperatures), cortical and VTA EEG, neck EMG activity, and locomotion in freely moving rats. Repeated injections of intravenous nicotine (30 μg/kg) induced sensitization of the drug's effects on all these measures. In contrast, repeated injections of the peripherally acting analog of nicotine, nicotine pyrrolidine methiodide (nicotinePM, 30 μg/kg, i.v.) resulted in habituation (tolerance) of the same physiological, neuronal, and behavioral measures. However, after repeated nicotine exposure, acute nicotinePM injections induced nicotine-like physiological responses: powerful cortical and VTA EEG desynchronization, EMG activation, a large brain temperature increase, but weaker hyperlocomotion. Additionally, both the acute locomotor response to nicotine and nicotine-induced locomotor sensitization were attenuated by blockade of peripheral nicotinic receptors by hexamethonium (3 mg/kg, i.v.). These data suggest that the peripheral actions of nicotine, which precede its direct central actions, serve as a conditioned interoceptive cue capable of eliciting nicotine-like physiological and neural responses after repeated nicotine exposure. Thus, by providing a neural signal to the CNS that is repeatedly paired with the direct central effects of nicotine, the drug's peripheral actions play a critical role in the development of nicotine-induced physiological, neural, and behavioral sensitization. PMID:23761889

  4. Pharmacologic characterization of a nicotine-discriminative stimulus in rhesus monkeys.

    PubMed

    Cunningham, Colin S; Javors, Martin A; McMahon, Lance R

    2012-06-01

    This study examined mechanisms by which nicotine (1.78 mg/kg base s.c.) produces discriminative stimulus effects in rhesus monkeys. In addition to nicotine, various test compounds were studied including other nicotinic acetylcholine receptor agonists (varenicline and cytisine), antagonists [mecamylamine and the α4β2 receptor-selective antagonist dihydro-β-erythroidine (DHβE)], a nicotinic acetylcholine receptor antagonist/indirect-acting catecholamine agonist (bupropion), and non-nicotinics (cocaine and midazolam). Nicotine, varenicline, and cytisine dose-dependently increased drug-lever responding; the ED(50) values were 0.47, 0.53, and 39 mg/kg, respectively. Bupropion and cocaine produced 100% nicotine-lever responding in a subset of monkeys, whereas mecamylamine, DHβE, and midazolam produced predominantly vehicle-lever responding. The training dose of nicotine resulted in 1128 ng/ml cotinine in saliva. Mecamylamine antagonized the discriminative stimulus effects of nicotine and varenicline, whereas DHβE was much less effective. Nicotine and varenicline had synergistic discriminative stimulus effects. In monkeys responding predominantly on the vehicle lever after a test compound (bupropion, cocaine, and midazolam), that test compound blocked the nicotine-discriminative stimulus, perhaps reflecting a perceptual-masking phenomenon. These results show that nicotine, varenicline, and cytisine produce discriminative stimulus effects through mecamylamine-sensitive receptors (i.e., nicotinic acetylcholine) in primates, whereas the involvement of DHβE-sensitive receptors (i.e., α4β2) is unclear. The current nicotine-discrimination assay did not detect a difference in agonist efficacy between nicotine, varenicline, and cytisine, but did show evidence of involvement of dopamine. The control that nicotine has over choice behavior can be disrupted by non-nicotinic compounds, suggesting that non-nicotinics could be exploited to decrease the control that tobacco has

  5. In vitro test of nicotine's permeability through human skin. Risk evaluation and safety aspects.

    PubMed

    Zorin, S; Kuylenstierna, F; Thulin, H

    1999-08-01

    Permeability tests with Franz' diffusion cells and an in vitro test model were made to evaluate the importance of dermal absorption of nicotine as a pathway for intoxication. Studies were carried out to ensure that safety procedures, when spilling nicotine on skin, are sufficient to prevent poisoning. Pure nicotine and nicotine in various concentrations in water or ethanol were applied on human skin or gloves in Franz' cells. Washing was simulated by removing nicotine from skin after 3 or 5 min. Permeation rate (flux) and lag time were calculated and estimated for human skin. Different glove materials were tested for their nicotine breakthrough time. Flux depended on concentration in a non-linear way when nicotine-water solutions were tested. Highest flux was found in 50% w/w nicotine dissolved in water. Solutions with low concentration of nicotine (1% w/w) dissolved in water had a similar permeation rate to 100% nicotine. Flux was found to be low when using ethanol as a vehicle; flux was also pH-dependent. The nicotine-water solution containing acetic acid had the lowest flux. The tests where nicotine was washed away revealed that skin served as a possible nicotine depot, because nicotine concentration in the receptor compartment continued to increase after removing the nicotine from the surface. The length of contact time affected the amount of substance passing the skin, resulting in great difference between 3 and 5 min contact time, 5 min giving higher nicotine concentration and 3 min lower. This emphasizes the importance of washing away nicotine spilled on skin rapidly. Two glove types were tested and they were found to be appropriate in their use with nicotine if changed regularly. PMID:10518466

  6. Nicotine as a Factor in Stress Responsiveness Among Detoxified Alcoholics

    PubMed Central

    Gilbertson, Rebecca; Frye, Reginald F.; Nixon, Sara Jo

    2011-01-01

    Aims: The effect of transdermal nicotine on stress reactivity was investigated in currently smoking, detoxified, substance-dependent individuals (65% alcohol dependent, n = 51; 31 male) following a psychosocial stressor. Methods: Using a randomized, double-blind, placebo-controlled design, subjects were assigned to receive either active transdermal nicotine (low or high dose) or placebo. Six hours following nicotine administration, subjects performed a laboratory psychosocial stressor consisting of two 4-min public-speaking sessions. Results: Consistent with prior reports, substance-dependent individuals displayed a blunted stress response. However, a review of the cortisol distribution data encouraged additional analyses. Notably, a significant minority of the substance-dependent individuals (33%) demonstrated elevated poststress cortisol levels. This group of responders was more likely to be alcohol dependent and to have received the high dose of nicotine [χ2(2) = 32, P < 0.0001], [χ2(2) = 18.66, P < 0.0001]. Differences in salivary cortisol responses between responders and nonresponders could not be accounted for by the length of sobriety, nicotine withdrawal levels, anxiety or depressive symptomatology at the time of the psychosocial stressor. Conclusion: These results suggest that nicotine administration may support a normalization of the salivary cortisol response following psychosocial stress in subgroups of substance-dependent individuals, particularly those who are alcohol dependent. Given the association between blunted cortisol levels and relapse, and the complex actions of nicotine at central and peripheral sites, these findings support the systematic study of factors including nicotine, which may influence stress reactivity and the recovery process in alcohol-dependent individuals. PMID:21045074

  7. Neonatal Nicotine Exposure Impairs Development of Auditory Temporal Processing

    PubMed Central

    Sun, Wei; Hansen, Anna; Zhang, Liyan; Lu, Jianzhong; Stolzberg, Daniel; Kraus, Kari Suzanne

    2008-01-01

    Accurate temporal processing of sound is essential for detecting word structures in speech. Maternal smoking affects speech processing in newborns and may influence child language development; however, it is unclear how neonatal exposure to nicotine, present in cigarettes, affects the normal development of temporal processing. The present study used the gap-induced prepulse inhibition (gap-PPI) of the acoustic startle response to investigate the effects of neonatal nicotine exposure on the normal development of gap detection, a behavioral testing procedure of auditory temporal resolution. Neonatal rats were injected twice per day with saline (control), 1 mg/kg nicotine (N-1mg) or 5 mg/kg nicotine (N-5mg) from postnatal day 8 to 12 (P8–P12). During the first month after birth, rats showed poor gap-PPI in all three groups. At P45 and P60, gap-PPI in control rats improved significantly, whereas rats exposed to nicotine exhibited less improvement. At P60, the gap-detection threshold in the N-5mg group was significantly higher than in the control group, suggesting that neonatal nicotine exposure affects the normal development of gap detection acuity. Additionally, 1 hour after receiving an acute nicotine injection (1 mg/kg), gap-PPI recorded in adult rats from the N-5mg group showed a temporary significant improvement. These results suggest that neonatal nicotine exposure reduces gap-PPI implying an impairment of the normal development of auditory temporal processing by inducing changes in cholinergic systems. PMID:18801421

  8. NMDA receptors regulate nicotine-enhanced brain reward function and intravenous nicotine self-administration: role of the ventral tegmental area and central nucleus of the amygdala.

    PubMed

    Kenny, Paul J; Chartoff, Elena; Roberto, Marisa; Carlezon, William A; Markou, Athina

    2009-01-01

    Nicotine is considered an important component of tobacco responsible for the smoking habit in humans. Nicotine increases glutamate-mediated transmission throughout brain reward circuitries. This action of nicotine could potentially contribute to its intrinsic rewarding and reward-enhancing properties, which motivate consumption of the drug. Here we show that the competitive N-methyl-D-aspartate (NMDA) receptor antagonist LY235959 (0.5-2.5 mg per kg) abolished nicotine-enhanced brain reward function, reflected in blockade of the lowering of intracranial self-stimulation (ICSS) thresholds usually observed after experimenter-administered (0.25 mg per kg) or intravenously self-administered (0.03 mg per kg per infusion) nicotine injections. The highest LY235959 dose (5 mg per kg) tested reversed the hedonic valence of nicotine from positive to negative, reflected in nicotine-induced elevations of ICSS thresholds. LY235959 doses that reversed nicotine-induced lowering of ICSS thresholds also markedly decreased nicotine self-administration without altering responding for food reinforcement, whereas the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonist NBQX had no effects on nicotine intake. In addition, nicotine self-administration upregulated NMDA receptor subunit expression in the central nucleus of the amygdala (CeA) and ventral tegmental area (VTA), suggesting important interactions between nicotine and the NMDA receptor. Furthermore, nicotine (1 microM) increased NMDA receptor-mediated excitatory postsynaptic currents in rat CeA slices, similar to its previously described effects in the VTA. Finally, infusion of LY235959 (0.1-10 ng per side) into the CeA or VTA decreased nicotine self-administration. Taken together, these data suggest that NMDA receptors, including those in the CeA and VTA, gate the magnitude and valence of the effects of nicotine on brain reward systems, thereby regulating motivation to consume the drug. PMID:18418357

  9. Early postnatal nicotine exposure causes hippocampus-dependent memory impairments in adolescent mice: association with altered nicotinic cholinergic modulation of LTP, but not impaired LTP

    PubMed Central

    Nakauchi, Sakura; Malvaez, Melissa; Su, Hailing; Kleeman, Elise; Dang, Richard; Wood, Marcelo A.; Sumikawa, Katumi

    2014-01-01

    Fetal nicotine exposure from smoking during pregnancy causes long-lasting cognitive impairments in offspring, yet little is known about the mechanisms that underlie this effect. Here we demonstrate that early postnatal exposure of mouse pups to nicotine via maternal milk impairs long-term, but not short-term, hippocampus-dependent memory during adolescence. At the Schaffer collateral (SC) pathway, the most widely studied synapses for a cellular correlate of hippocampus-dependent memory, the induction of N-methyl-d-aspartate receptor-dependent transient long-term potentiation (LTP) and protein synthesis-dependent long-lasting LTP are not diminished by nicotine exposure, but rather unexpectedly the threshold for LTP induction becomes lower after nicotine treatment. Using voltage sensitive dye to visualize hippocampal activity, we found that early postnatal nicotine exposure also results in enhanced CA1 depolarization and hyperpolarization after SC stimulation. Furthermore, we show that postnatal nicotine exposure induces pervasive changes to the nicotinic modulation of CA1 activity: activation of nicotinic receptors no longer increases CA1 network depolarization, acute nicotine inhibits rather than facilitates the induction of LTP at the SC pathway by recruiting an additional nicotinic receptor subtype, and acute nicotine no longer blocks LTP induction at the temporoammonic pathway. These findings reflect the pervasive impact of nicotine exposure during hippocampal development, and demonstrate an association of hippocampal memory impairments with altered nicotinic cholinergic modulation of LTP, but not impaired LTP. The implication of our results is that nicotinic cholinergic-dependent plasticity is required for long-term memory formation and that postnatal nicotine exposure disrupts this form of plasticity. PMID:25545599

  10. α3β4 nicotinic acetylcholine receptors in the medial habenula modulate the mesolimbic dopaminergic response to acute nicotine in vivo.

    PubMed

    McCallum, Sarah E; Cowe, Matthew A; Lewis, Samuel W; Glick, Stanley D

    2012-09-01

    Habenulo-interpeduncular nicotinic receptors, particularly those containing α3, β4 and α5 subunits, have recently been implicated in the reinforcing effects of nicotine. Our laboratory has shown that injection of α3β4 nicotinic receptor antagonists into the medial habenula (MHb) decreases self-administration of multiple abused drugs, including nicotine (Glick et al., 2006, 2008; 2011). However, it is unclear whether blockade of MHb nicotinic receptors has a direct effect on mesolimbic dopamine. Here, we performed in vivo microdialysis in female rats. Microdialysis probes were implanted into the nucleus accumbens (NAcc) and α3β4 nicotinic receptor antagonists (18-methoxycoronaridine; 18-MC or α-conotoxin AuIB; AuIB), were injected into the ipsilateral MHb, just prior to systemic nicotine (0.4 mg/kg, s.c.). Dialysate samples were collected before and after drug administration and levels of extracellular dopamine and its metabolites were measured using HPLC. Acute nicotine administration increased levels of extracellular dopamine and its metabolites in the NAcc. Pre-treatment with intra-habenular AuIB or 18-MC prevented nicotine-induced increases in accumbal dopamine. Neither drug had an effect on nicotine-induced increases in dopamine metabolites, suggesting that α3β4 receptors do not play a role in dopamine metabolism. The effect of intra-habenular blockade of α3β4 receptors on NAcc dopamine was selective for acute nicotine: neither AuIB nor 18-MC prevented increases in NAcc dopamine stimulated by acute d-amphetamine or morphine. These results suggest the mesolimbic response to acute nicotine, but not to acute administration of other drugs of abuse, is directly modulated by α3β4 nicotinic receptors in the MHb, and emphasize a critical role for habenular nicotinic receptors in nicotine's reinforcing effects. PMID:22561751

  11. Phase equilibria in the system BN-Si{sub 3}N{sub 4}-Mg{sub 3}N{sub 2} at atmospheric and high pressures

    SciTech Connect

    Zhukov, A.N.; Burdina, K.P.; Semenenko, K.N.

    1995-01-20

    Isothermal sections for the system BN-Si{sup 3}N{sup 4}-Mg{sub 3}N{sub 2} at atmospheric and 5.0 GPa pressures have been constructed. Three new compounds Mg{sub 5}Si{sub 2}N{sub 6}, Mg{sub 7}SiB{sub 2}N{sub 8}, and Mg{sub 10}SiBN{sub 9} have been found, the first two of which are formed both at atmospheric and at high pressure and the last only at high pressure. P,T parameters of the {alpha}-BN {r_arrow} {beta}-BN conversion in the presence of Mg{sub 7}SiB{sub 2}N{sub 8} and MgSiN{sub 2} have been determined. 13 refs., 3 figs., 4 tabs.

  12. Concentration of Nicotine and Glycols in 27 Electronic Cigarette Formulations.

    PubMed

    Peace, Michelle R; Baird, Tyson R; Smith, Nathaniel; Wolf, Carl E; Poklis, Justin L; Poklis, Alphonse

    2016-07-01

    Personal battery-powered vaporizers or electronic cigarettes were developed to deliver a nicotine vapor such that smokers could simulate smoking tobacco without the inherent pathology of inhaled tobacco smoke. Electronic cigarettes and their e-cigarette liquid formulations are virtually unregulated. These formulations are typically composed of propylene glycol and/or glycerin, flavoring components and an active drug, such as nicotine. Twenty-seven e-cigarette liquid formulations that contain nicotine between 6 and 22 mg/L were acquired within the USA and analyzed by various methods to determine their contents. They were screened by Direct Analysis in Real Time™ Mass Spectrometry (DART-MS). Nicotine was confirmed and quantitated by high-performance liquid chromatography-tandem mass spectrometry, and the glycol composition was confirmed and quantitated by gas chromatography-mass spectrometry. The DART-MS screening method was able to consistently identify the exact mass peaks resulting from the protonated molecular ion of nicotine, glycol and a number of flavor additives within 5 mmu. Nicotine concentrations were determined to range from 45 to 131% of the stated label concentration, with 18 of the 27 have >10% variance. Glycol composition was generally accurate to the product description, with only one exception where the propylene glycol to glycerin percentage ratio was stated as 50:50 and the determined concentration of propylene glycol to glycerin was 81:19 (% v/v). No unlabeled glycols were detected in these formulations. PMID:27165804

  13. Disruption of nicotine conditioning by dopamine D(3) receptor ligands.

    PubMed

    Le Foll, B; Schwartz, J-C; Sokoloff, P

    2003-02-01

    Tobacco smoking is the first cause of preventable death in modern countries. Nicotine replacement therapy or sustained release bupropion helps smoking cessation, but relapse rates are still very high. Nicotine, like other drugs of abuse, activates the dopamine mesolimbic system, which originates in the ventral tegmental area and projects notably to the nucleus accumbens. Situations or environmental stimuli previously associated with cigarette smoking, for example, smell of cigarette smoke, can elicit craving in abstinent smokers and promote relapse. Reducing the effects of nicotine-associated cues might therefore have potential therapeutic utility for smoking cessation. Such an approach has been validated for cocaine in animals, by using the dopamine D(3) receptor-selective partial agonist BP 897, which inhibits cocaine cue-induced drug-seeking behavior. Here we show that rats repeatedly injected with nicotine in a particular environment develop nicotine-conditioned locomotor responses, accompanied by an increase in D(3) receptor expression in the nucleus accumbens. This conditioned behavior was inhibited by BP 897 or a selective D(3) receptor antagonist, suggesting that antagonizing dopamine selectively at the D(3) receptor disrupts nicotine-conditioned effects and might represent a novel therapeutic approach for smoking cessation. PMID:12610655

  14. The effect of transdermal nicotine patches on sleep and dreams.

    PubMed

    Page, F; Coleman, G; Conduit, R

    2006-07-30

    This study was undertaken to determine the effect of 24-h transdermal nicotine patches on sleep and dream mentation in 15 smokers aged 20 to 33. Utilising a repeated measures design, it was found that more time awake and more ASDA micro-arousals occurred while wearing the nicotine patch compared to placebo. Also, the percentage of REM sleep decreased, but REM latency and the proportion of time spent in NREM sleep stages did not change significantly. Dream reports containing visual imagery, visual imagery ratings and the number of visualizable nouns were significantly greater from REM compared to Stage 2 awakenings, regardless of patch condition. However, a general interaction effect was observed. Stage 2 dream variables remained equivalent across nicotine and placebo conditions. Within REM sleep, more dream reports containing visual imagery occurred while wearing the nicotine patch, and these were rated as more vivid. The greater frequency of visual imagery reports and higher imagery ratings specifically from REM sleep suggests that previously reported dreaming side effects from 24-h nicotine patches may be specific to REM sleep. Combined with previous animal studies showing that transdermally delivered nicotine blocks PGO activity in REM sleep, the current results do no appear consistent with PGO-based hypotheses of dreaming, such as the Activation-Synthesis (AS) or Activation, Input and Modulation (AIM) models. PMID:16782142

  15. Nicotine effect on cardiovascular system and ion channels.

    PubMed

    Hanna, Salma Toma

    2006-03-01

    Smoking is a leading cause of cardiovascular disease, hypertension, myocardial infarction, and stroke. Nicotine is one of the components of cigarette smoke. Nicotine effects on the cardiovascular system reflect the activity of the nicotine receptors centrally and on peripheral autonomic ganglia. It has been found that cigarette smoke extract-induced contraction of porcine coronary arteries is related to superoxide anion-mediated degradation of nitric oxide. Treatment of rabbit aortas with an oxygen free radicals scavenger attenuated cigarette smoke impairment of arterial relaxation. Treatment of smokers with vitamin C, an antioxidant, improved impaired endothelium-dependent reactivity of large peripheral arteries. Thus it appears that chronic smoking and acute exposure to cigarette smoke extract may alter endothelium-dependent reactivity via the production of oxygen derived free radicals. This review discusses the effects of nicotine on resistance arterioles, compliance arteries, smooth muscle cells, and ion channels in the cardiovascular system. We discuss studies performed on humans, nicotine-exposed animals, and cell cultures yielding varying and inconsistent results that may be due to differences in experimental design, species, and the dose of exposure. Nicotine exposure appears to induce a combination of free radical production, vascular wall adhesion, and a reduction of fibrinolytic activity in the plasma. PMID:16633075

  16. Transdermal Nicotine Application Attenuates Cardiac Dysfunction after Severe Thermal Injury

    PubMed Central

    Claassen, Leif; Papst, Stephan; Reimers, Kerstin; Stukenborg-Colsman, Christina; Steinstraesser, Lars; Vogt, Peter M.; Kraft, Theresia; Niederbichler, Andreas D.

    2015-01-01

    Background. Severe burn trauma leads to an immediate and strong inflammatory response inciting cardiac dysfunction that is associated with high morbidity and mortality. The aim of this study was to determine whether transdermal application of nicotine could influence the burn-induced cardiac dysfunction via its known immunomodulatory effects. Material and Methods. A standardized rat burn model was used in 35 male Sprague Dawley rats. The experimental animals were divided into a control group, a burn trauma group, a burn trauma group with additional nicotine treatment, and a sham group with five experimental animals per group. The latter two groups received nicotine administration. Using microtip catheterization, functional parameters of the heart were assessed 12 or 24 hours after infliction of burn trauma. Results. Burn trauma led to significantly decreased blood pressure (BP) values whereas nicotine administration normalized BP. As expected, burn trauma also induced a significant deterioration of myocardial contractility and relaxation parameters. After application of nicotine these adverse effects were attenuated. Conclusion. The present study showed that transdermal nicotine administration has normalizing effects on burn-induced myocardial dysfunction parameters. Further research is warranted to gain insight in molecular mechanisms and pathways and to evaluate potential treatment options in humans. PMID:26290866

  17. Associations between nicotine dependence, anhedonia, urgency and smoking motives.

    PubMed

    Roys, Melanie; Weed, Keri; Carrigan, Maureen; MacKillop, James

    2016-11-01

    Models of nicotine dependence have suggested that the association between urgency, a subconstruct of impulsivity, and smoking behaviors may be mediated by motivations. Motives that are driven by expectations that smoking will relieve negative affect or increase positive affect may be especially salient in persons who have depression symptoms such as anhedonia. Support for associations between symptoms of depression, urgency, and addiction has been found for alcohol dependence, but empirical analysis is lacking for an interactive effect of urgency and depression symptoms on nicotine dependence. The current study investigated relationships among the urgency facet of impulsivity, anhedonia, smoking motives, and nicotine dependence with secondary analyses of a sample of 1084 daily smokers using simultaneous moderation and multiple mediation analyses. The moderation analysis revealed that although urgency was significantly associated with smoking at average or higher levels of anhedonia, it was unrelated to smoking when few anhedonia symptoms were endorsed. Further, multiple mediation analyses revealed that the smoking motives of craving, cue exposure, positive reinforcement, and tolerance significantly mediated the relationship between urgency and nicotine dependence. Results suggest that models of alcohol addiction that include an interactive effect of urgency and certain symptoms of depression may be applied to nicotine dependence. Examination of the multiple mediational pathways between urgency and nicotine dependence suggests directions for intervention efforts. PMID:27376882

  18. Nicotinic Receptors: Role in Addiction and Other Disorders of the Brain

    PubMed Central

    Sharma, Geeta; Vijayaraghavan, Sukumar

    2008-01-01

    Nicotine, the addictive component of cigarette smoke has profound effects on the brain. Activation of its receptors by nicotine has complex consequences for network activity throughout the brain, potentially contributing to the addictive property of the drug. Nicotinic receptors have been implicated in psychiatric illnesses like schizophrenia and are also neuroprotective, potentially beneficial for neurodegenerative diseases. These effects of nicotine serve to emphasize the multifarious roles the drug, acting through multiple nicotinic acetylcholine receptor subtypes. The findings also remind us of the complexity of signaling mechanisms and stress the risks of unintended consequences of drugs designed to combat nicotine addiction. PMID:20148179

  19. Perinatal nicotine exposure induces asthma in second generation offspring

    PubMed Central

    2012-01-01

    Background By altering specific developmental signaling pathways that are necessary for fetal lung development, perinatal nicotine exposure affects lung growth and differentiation, resulting in the offsprings' predisposition to childhood asthma; peroxisome proliferator-activated receptor gamma (PPARγ) agonists can inhibit this effect. However, whether the perinatal nicotine-induced asthma risk is restricted to nicotine-exposed offspring only; whether it can be transmitted to the next generation; and whether PPARγ agonists would have any effect on this process are not known. Methods Time-mated Sprague Dawley rat dams received either placebo or nicotine (1 mg/kg, s.c.), once daily from day 6 of gestation to postnatal day (PND) 21. Following delivery, at PND21, generation 1 (F1) pups were either subjected to pulmonary function tests, or killed to obtain their lungs, tracheas, and gonads to determine the relevant protein markers (mesenchymal contractile proteins), global DNA methylation, histone 3 and 4 acetylation, and for tracheal tension studies. Some F1 animals were used as breeders to generate F2 pups, but without any exposure to nicotine in the F1 pregnancy. At PND21, F2 pups underwent studies similar to those performed on F1 pups. Results Consistent with the asthma phenotype, nicotine affected lung function in both male and female F1 and F2 offspring (maximal 250% increase in total respiratory system resistance, and 84% maximal decrease in dynamic compliance following methacholine challenge; P < 0.01, nicotine versus control; P < 0.05, males versus females; and P > 0.05, F1 versus F2), but only affected tracheal constriction in males (51% maximal increase in tracheal constriction following acetylcholine challenge, P < 0.01, nicotine versus control; P < 0.0001, males versus females; P > 0.05, F1 versus F2); nicotine also increased the contractile protein content of whole lung (180% increase in fibronectin protein levels, P < 0.01, nicotine versus control, and P

  20. Nicotine Dehydrogenase Complexed with 6-Hydroxypseudooxynicotine Oxidase Involved in the Hybrid Nicotine-Degrading Pathway in Agrobacterium tumefaciens S33

    PubMed Central

    Li, Huili; Xie, Kebo; Yu, Wenjun; Hu, Liejie; Huang, Haiyan; Xie, Huijun

    2016-01-01

    Nicotine, a major toxic alkaloid in tobacco wastes, is degraded by bacteria, mainly via pyridine and pyrrolidine pathways. Previously, we discovered a new hybrid of the pyridine and pyrrolidine pathways in Agrobacterium tumefaciens S33 and characterized its key enzyme 6-hydroxy-3-succinoylpyridine (HSP) hydroxylase. Here, we purified the nicotine dehydrogenase initializing the nicotine degradation from the strain and found that it forms a complex with a novel 6-hydroxypseudooxynicotine oxidase. The purified complex is composed of three different subunits encoded by ndhAB and pno, where ndhA and ndhB overlap by 4 bp and are ∼26 kb away from pno. As predicted from the gene sequences and from chemical analyses, NdhA (82.4 kDa) and NdhB (17.1 kDa) harbor a molybdopterin cofactor and two [2Fe-2S] clusters, respectively, whereas Pno (73.3 kDa) harbors an flavin mononucleotide and a [4Fe-4S] cluster. Mutants with disrupted ndhA or ndhB genes did not grow on nicotine but grew well on 6-hydroxynicotine and HSP, whereas the pno mutant did not grow on nicotine or 6-hydroxynicotine but grew well on HSP, indicating that NdhA and NdhB are responsible for initialization of nicotine oxidation. We successfully expressed pno in Escherichia coli and found that the recombinant Pno presented 2,6-dichlorophenolindophenol reduction activity when it was coupled with 6-hydroxynicotine oxidation. The determination of reaction products catalyzed by the purified enzymes or mutants indicated that NdhAB catalyzed nicotine oxidation to 6-hydroxynicotine, whereas Pno oxidized 6-hydroxypseudooxynicotine to 6-hydroxy-3-succinoylsemialdehyde pyridine. These results provide new insights into this novel hybrid pathway of nicotine degradation in A. tumefaciens S33. PMID:26729714

  1. PRENATAL NICOTINE EXPOSURE SELECTIVELY AFFECTS NICOTINIC RECEPTOR EXPRESSION IN PRIMARY AND ASSOCIATIVE VISUAL CORTICES OF THE FETAL BABOON

    PubMed Central

    Duncan, Jhodie R.; Garland, Marianne; Stark, Raymond I.; Myers, Michael M.; Fifer, William P.; Mokler, David J.; Kinney, Hannah C.

    2014-01-01

    Exposure to nicotine during pregnancy via maternal cigarette smoking is associated with visual deficits in children. This is possibly due to activation of nicotinic acetylcholine receptors (nAChRs) in the occipital cortex which are important in the development of visual mapping. Using a baboon model we explored the effects of prenatal nicotine on parameters in the primary and associated visual cortices. Pregnant baboons were infused with nicotine (0.5 mg/hr, i.v.) or saline from 86 days gestation. At 161 days gestation fetal brains were collected (n=5/group) and the occipital lobe assessed for nAChRs and markers of the serotonergic and catecholaminergic systems using tissue autoradiography and/or high performance liquid chromatography. Neuronal nAChRs and serotonergic markers were expressed in a region and subunit dependent manner. Prenatal nicotine exposure was associated with increased binding for 3H-epibatidine sensitive nAChRs in the primary visual cortex (BA 17) and BA 18, but not BA 19, of the associative visual cortex (p<0.05). Markers of the serotonergic or catecholaminergic systems were not significantly altered. Thus, prenatal nicotine exposure is associated with alterations in the cholinergic system in the occipital lobe which may aid in the explanation of the appearance of visual deficits in children from mothers who smoke during pregnancy. PMID:24903536

  2. A simple physiologically based pharmacokinetic model evaluating the effect of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans.

    PubMed

    Saylor, Kyle; Zhang, Chenming

    2016-09-15

    Physiologically based pharmacokinetic (PBPK) modeling was applied to investigate the effects of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans. Successful construction of both rat and human models was achieved by fitting model outputs to published nicotine concentration time course data in the blood and in the brain. Key parameters presumed to have the most effect on the ability of these antibodies to prevent nicotine from entering the brain were selected for investigation using the human model. These parameters, which included antibody affinity for nicotine, antibody cross-reactivity with cotinine, and antibody concentration, were broken down into different, clinically-derived in silico treatment levels and fed into the human PBPK model. Model predictions suggested that all three parameters, in addition to smoking status, have a sizable impact on anti-nicotine antibodies' ability to prevent nicotine from entering the brain and that the antibodies elicited by current human vaccines do not have sufficient binding characteristics to reduce brain nicotine concentrations. If the antibody binding characteristics achieved in animal studies can similarly be achieved in human studies, however, nicotine vaccine efficacy in terms of brain nicotine concentration reduction is predicted to meet threshold values for alleviating nicotine dependence. PMID:27473014

  3. Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure

    SciTech Connect

    Menelaou, Evdokia; Paul, Latoya T.; Perera, Surangi N.; Svoboda, Kurt R.

    2015-04-01

    Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMNs). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30 μM). Previous work showed that the paralytic mutant zebrafish known as sofa potato exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. - Highlights: • Embryonic nicotine exposure can specifically affect secondary motoneuron axons in a dose-dependent manner.

  4. Blockade of Dopamine D4 Receptors Attenuates Reinstatement of Extinguished Nicotine-Seeking Behavior in Rats

    PubMed Central

    Yan, Yijin; Pushparaj, Abhiram; Le Strat, Yann; Gamaleddin, Islam; Barnes, Chanel; Justinova, Zuzana; Goldberg, Steven R; Le Foll, Bernard

    2012-01-01

    Since cloning of the dopamine receptor D4 (DRD4), its role in the brain has remained unclear. It has been reported that polymorphism of the DRD4 gene in humans is associated with reactivity to cues related to tobacco smoking. However, the role of DRD4 in animal models of nicotine addiction has seldom been explored. In our study, male Long-Evans rats learned to intravenously self-administer nicotine under a fixed-ratio (FR) schedule of reinforcement. Effects of the selective DRD4 antagonist L-745,870 were evaluated on nicotine self-administration behavior and on reinstatement of extinguished nicotine-seeking behavior induced by nicotine-associated cues or by priming injections of nicotine. L-745,870 was also tested on reinstatement of extinguished food-seeking behavior as a control. In addition, the selective DRD4 agonist PD 168,077 was tested for its ability to reinstate extinguished nicotine-seeking behavior. Finally, L-745,870 was tested in Sprague Dawley rats trained to discriminate administration of 0.4 mg/kg nicotine from vehicle under an FR schedule of food delivery. L-745,870 significantly attenuated reinstatement of nicotine-seeking induced by both nicotine-associated cues and nicotine priming. In contrast, L-745,870 did not affect established nicotine self-administration behavior or reinstatement of food-seeking behavior induced by food cues or food priming. L-745,870 did not produce nicotine-like discriminative-stimulus effects and did not alter discriminative-stimulus effects of nicotine. PD 168,077 did not reinstate extinguished nicotine-seeking behavior. As DRD4 blockade by L-745,870 selectively attenuated both cue- and nicotine-induced reinstatement of nicotine-seeking behavior, without affecting cue- or food-induced reinstatement of food-seeking behavior, DRD4 antagonists are potential therapeutic agents against tobacco smoking relapse. PMID:22030716

  5. CYP2A6 Polymorphisms May Strengthen Individualized Treatment for Nicotine Dependence

    PubMed Central

    Akrodou, Yawo Mawuli

    2015-01-01

    Each CYP2A6 gene variant metabolizes nicotine differently depending on its enzymatic activities. The normal nicotine metabolizer CYP2A6*1A is associated with high scores of nicotine dependence (5–10) on the Fagerström Test for Nicotine Dependence (FTND) scale because it encodes for enzymes that catalyze nicotine 100%. Slow nicotine metabolizers (i.e., CYP2A6*1H, CYP2A6*4A, CYP2A6*9, and CYP2A6*12A) are associated with underrated nicotine metabolizing activity (50%–75%), linking them to low scores for nicotine dependence (0–4) on the FTND scale. In a clinical trial involving the use of bupropion, people who were carriers of slow nicotine metabolizers were found to have a tendency to maintain abstinence 1.7 times longer than people with normal nicotine metabolizers. An overview of CYP2A6 polymorphism enzymatic activities in nicotine dependence etiology and treatment revealed that slow nicotine metabolizers may strengthen the individualized treatment of nicotine dependence. PMID:26060595

  6. Reversal of the gastric effects of nicotine by nitric oxide donor treatment.

    PubMed

    Ma, J J; Hou, D Q; Zhang, Q B; Korsten, M A

    2001-01-01

    Nicotine intensifies experimental gastric ulceration by reducing gastric mucosal blood flow (GMBF) and mucus. As both these parameters can be improved by nitric oxide (NO), we evaluated the impact of a NO donor in ethanol-induced gastric mucosal injury in rats administered nicotine. A nicotine solution or water was administered for 20 days to Sprague-Dawley rats. NO donor (isosorbide dinitrate) was given 60 and 10 min before preparation of ex vivo gastric chambers and exposure to ethanol. Chronic nicotine intake significantly reduced GMBF and gastric mucus content. Nicotine intensifies ethanol-induced gastric injury and short-term administration of NO donor failed to antagonize the ulcerogenic action from either nicotine or alcohol. In another study, rats drank nicotine solution for 20 days, after which the nicotine was withdrawn and replaced by water for 10 additional days. NO donor was provided during these last 10 days. The gastric effects of nicotine persisted for at least 10 days after nicotine was withdrawn but then these effects could be abolished by prolonged NO treatment. Nicotine reduces plasma nitrite level, but gastric mucosal MPO activity remained unchanged. Our data suggest that nicotine cessation plus a longer period of NO donor administration can completely abolish the gastric effects of nicotine. PMID:11244248

  7. Propensity for social interaction predicts nicotine-reinforced behaviors in outbred rats.

    PubMed

    Wang, T; Han, W; Wang, B; Jiang, Q; Solberg-Woods, L C; Palmer, A A; Chen, H

    2014-02-01

    Social and genetic factors can influence smoking behavior. Using olfactogustatory stimuli as the sensory cue for intravenous nicotine self-administration (SA), we previously showed that social learning of nicotine contingent odor cue prevented rats from developing conditioned taste aversion and allowed them to instead establish stable nicotine SA. We hypothesized that genetic factors influenced socially acquired nicotine SA. A heterogeneous stock (HS; N/NIH) of outbred rats was trained to self-administer nicotine using the social learning protocol. Both male and female HS rats acquired nicotine SA, but females self-administered more nicotine than males. After extinction, the context previously paired with nicotine SA, in conjunction with socially transmitted drug cues, was sufficient to cause reinstatement of drug-seeking behavior. Wide variation in both nicotine intake and reinstatement was observed. Using multiple regression analysis, we found that measures of social interaction were significant predictors of nicotine intake and reinstatement of drug seeking in both males and females. Furthermore, measures of depression were predictors of nicotine intake in both males and females, anxiety was a predictor only in males and response to novelty was a predictor only in females. In males, measures of both depression and anxiety predicted nicotine reinstatement. Together, these data supported the ideas that genetically determined propensities for emotional and social phenotypes are significant determinants for nicotine-reinforced behavior, and that the HS rat is a suitable tool for dissecting genetic mechanisms that may underlie the interaction between social behavior, anxiety, depression and smoking. PMID:24289793

  8. Differences in Nicotine Metabolism of Two Nicotiana attenuata Herbivores Render Them Differentially Susceptible to a Common Native Predator

    PubMed Central

    Kumar, Pavan; Rathi, Preeti; Schöttner, Matthias; Baldwin, Ian T.; Pandit, Sagar

    2014-01-01

    Background Nicotiana attenuata is attacked by larvae of both specialist (Manduca sexta) and generalist (Spodoptera exigua) lepidopteran herbivores in its native habitat. Nicotine is one of N. attenuata's important defenses. M. sexta is highly nicotine tolerant; whether cytochrome P450 (CYP)-mediated oxidative detoxification and/or rapid excretion is responsible for its exceptional tolerance remains unknown despite five decades of study. Recently, we demonstrated that M. sexta uses its nicotine-induced CYP6B46 to efflux midgut-nicotine into the hemolymph, facilitating nicotine exhalation that deters predatory wolf spiders (Camptocosa parallela). S. exigua's nicotine metabolism is uninvestigated. Methodology/Principal Findings We compared the ability of these two herbivores to metabolize, tolerate and co-opt ingested nicotine for defense against the wolf spider. In addition, we analyzed the spider's excretion to gain insights into its nicotine metabolism. Contrary to previous reports, we found that M. sexta larvae neither accumulate the common nicotine oxides (cotinine, cotinine N-oxide and nicotine N-oxide) nor excrete them faster than nicotine. In M. sexta larvae, ingestion of nicotine as well as its oxides increases the accumulation of CYP6B46 transcripts. In contrast, S. exigua accumulates nicotine oxides and exhales less (66%) nicotine than does M. sexta. Spiders prefer nicotine-fed S. exigua over M. sexta, a preference reversed by topical or headspace nicotine supplementation, but not ingested or topically-coated nicotine oxides, suggesting that externalized nicotine but not the nicotine detoxification products deter spider predation. The spiders also do not accumulate nicotine oxides. Conclusions Nicotine oxidation reduces S. exigua's headspace-nicotine and renders it more susceptible to predation by spiders than M. sexta, which exhales unmetabolized nicotine. These results are consistent with the hypothesis that generalist herbivores incur costs of

  9. Effects of nicotine in combination with drugs described as positive allosteric nicotinic acetylcholine receptor modulators in vitro: discriminative stimulus and hypothermic effects in mice.

    PubMed

    Moerke, Megan J; de Moura, Fernando B; Koek, Wouter; McMahon, Lance R

    2016-09-01

    Some drugs that are positive allosteric nAChR modulators in vitro, desformylflustrabromine (dFBr), PNU-120596 and LY 2087101, have not been fully characterized in vivo. These drugs were examined for their capacity to share or modify the hypothermic and discriminative stimulus effects of nicotine (1mg/kg s.c.) in male C57Bl/6J mice. Nicotine, dFBr, and PNU-120596 produced significant hypothermia, whereas LY 2087101 (up to 100mg/kg) did not. Nicotine dose-dependently increased nicotine-appropriate responding and decreased response rate; the respective ED50 values were 0.56mg/kg and 0.91mg/kg. The modulators produced no more than 38% nicotine-appropriate responding up to doses that disrupted operant responding. Rank order potency was the same for hypothermia and rate-decreasing effects: nicotine>dFBr>PNU-120596=LY 2087101. Mecamylamine and the α4β2 nAChR antagonist dihydro-β-erythroidine, but not the α7 antagonist methyllycaconitine, antagonized the hypothermic effects of nicotine. In contrast, mecamylamine did not antagonize the hypothermic effects of the modulators. The combined discriminative stimulus effects of DFBr and nicotine were synergistic, whereas the combined hypothermic effects of nicotine with either dFBr or PNU-120596 were infra-additive. PNU-120596 did not modify the nicotine discriminative stimulus, and LY 2087101 did not significantly modify either effect of nicotine. Positive modulation of nicotine at nAChRs by PNU-120596 and LY 2087101 in vitro does not appear to confer enhancement of the nAChR-mediated hypothermic or discriminative stimulus effects of nicotine. However, dFBr appears to be a positive allosteric modulator of some behavioral effects of nicotine at doses of dFBr smaller than the doses producing unwanted effects (e.g. hypothermia) through non-nAChR mechanisms. PMID:27238974

  10. Effects of nicotine on rat sternohyoid muscle contractile properties.

    PubMed

    O'Halloran, Ken D

    2006-02-28

    Obstructive sleep apnoea (OSA) is a major clinical disorder characterised by recurring episodes of pharyngeal collapse during sleep. At present, there remains no satisfactory treatment for OSA. Pharmacological therapies as a potential treatment for the disorder are an attractive option and include agents that increase the contractility of the pharyngeal muscles. The aim of the present study was to examine the effects of nicotine on upper airway muscle contractile properties. In vitro isometric contractile properties were determined using strips of rat sternohyoid muscle in physiological salt solution containing nicotine (0-100 microg/ml) at 25 degrees C. Isometric twitch and tetanic tension, contraction time, half-relaxation time and tension-frequency relationship were determined by electrical field stimulation with platinum electrodes. Fatigue was induced by stimulation at 40 Hz with 300 ms trains at a frequency of 0.5 Hz for 5 min. Nicotine at a concentration of 1 microg/ml was associated with a significant increase in sternohyoid muscle specific tension compared to control data. Dose-dependent increases in contractile tension were not observed. Nicotine had effects on tension-frequency relationship and endurance properties of the sternohyoid muscle at some but not all doses. A leftward shift in the tension-frequency relationship was observed at low stimulus frequencies (20-30 Hz) for nicotine at a concentration of 1 and 5 microg/ml and a significant increase in fatigue resistance was observed with nicotine at a concentration of 10 microg/ml. As fatigue of the upper airway muscles has been implicated in obstructive airway conditions, a pharmacological agent that improves muscle endurance may prove useful as a potential treatment for such disorders. Therefore, further studies of the effects of nicotinic agonists on upper airway function are warranted. PMID:15994135

  11. The effects of acute nicotine on contextual safety discrimination.

    PubMed

    Kutlu, Munir G; Oliver, Chicora; Gould, Thomas J

    2014-11-01

    Anxiety disorders, such as post-traumatic stress disorder (PTSD), may be related to an inability to distinguish safe versus threatening environments and to extinguish fear memories. Given the high rate of cigarette smoking in patients with PTSD, as well as the recent finding that an acute dose of nicotine impairs extinction of contextual fear memory, we conducted a series of experiments to investigate the effect of acute nicotine in an animal model of contextual safety discrimination. Following saline or nicotine (at 0.0275, 0.045, 0.09 and 0.18 mg/kg) administration, C57BL/6J mice were trained in a contextual discrimination paradigm, in which the subjects received presentations of conditioned stimuli (CS) that co-terminated with a foot-shock in one context (context A (CXA)) and only CS presentations without foot-shock in a different context (context B (CXB)). Therefore, CXA was designated as the 'dangerous context', whereas CXB was designated as the 'safe context'. Our results suggested that saline-treated animals showed a strong discrimination between dangerous and safe contexts, while acute nicotine dose-dependently impaired contextual safety discrimination (Experiment 1). Furthermore, our results demonstrate that nicotine-induced impairment of contextual safety discrimination learning was not a result of increased generalized freezing (Experiment 2) or contingent on the common CS presentations in both contexts (Experiment 3). Finally, our results show that increasing the temporal gap between CXA and CXB during training abolished the impairing effects of nicotine (Experiment 4). The findings of this study may help link nicotine exposure to the safety learning deficits seen in anxiety disorder and PTSD patients. PMID:25271215

  12. Sorption, desorption, and surface oxidative fate of nicotine.

    PubMed

    Petrick, Lauren; Destaillats, Hugo; Zouev, Irena; Sabach, Sara; Dubowski, Yael

    2010-09-21

    Nicotine dynamics in an indoor environment can be greatly affected by building parameters (e.g. relative humidity (RH), air exchange rate (AER), and presence of ozone), as well as surface parameters (e.g. surface area (SA) and polarity). To better understand the indoor fate of nicotine, these parameter effects on its sorption, desorption, and oxidation rates were investigated on model indoor surfaces that included fabrics, wallboard paper, and wood materials. Nicotine sorption under dry conditions was enhanced by higher SA and higher polarity of the substrate. Interestingly, nicotine sorption to cotton and nylon was facilitated by increased RH, while sorption to polyester was hindered by it. Desorption was affected by RH, AER, and surface type. Heterogeneous nicotine-ozone reaction was investigated by Fourier transform infrared spectrometry with attenuated total reflection (FTIR-ATR), and revealed a pseudo first-order surface reaction rate of 0.035 +/- 0.015 min(-1) (at [O(3)] = 6 +/- 0.3 x 10(15) molecules cm(-3)) that was partially inhibited at high RH. Extrapolation to a lower ozone level ([O(3)] = 42 ppb) showed oxidation on the order of 10(-5) min(-1) corresponding to a half-life of 1 week. In addition, similar surface products were identified in dry and high RH using gas chromatography-mass spectrometry (GC-MS). However, FTIR analysis revealed different product spectra for these conditions, suggesting additional unidentified products and association with surface water. Knowing the indoor fate of condensed and gas phase nicotine and its oxidation products will provide a better understanding of nicotine's impact on personal exposures as well as overall indoor air quality. PMID:20582338

  13. Chronic forced swim stress produces subsensitivity to nicotine.

    PubMed

    Peck, J A; Dilsaver, S C; McGee, M

    1991-03-01

    Twice daily injections of saline reduce the thermic response to nicotine in the rat. The authors hypothesized that this was due to the stress of twice-daily handling and injection. However, the injection of saline is not a classic stressor. The hypothesis that stress blunts thermic responsiveness to nicotine was, therefore, tested using a classic form of chronic inescapable stress. Rats (n = 12) were subjected to a 14-day, twice daily course of inescapable cold water swim stress using a repeated measures design. Thermic responsiveness of nicotine was measured at baseline and every 7 days thereafter for 49 days. The mean response to nicotine (1.0 mg/kg IP) differed significantly across time, F(7,88) = 10.6, p less than 0.0001. Mean thermic responsiveness (+/- SEM) decreased from -0.75 +/- 0.09 at baseline to -0.41 +/- 0.18 degrees C (54.7% of baseline) following 14 days of forced swim stress. This change was not significant. However, the thermic response to nicotine was -0.14 +/- 0.13 degrees C (p less than 0.05), +0.55 +/- 0.12 degrees C (p less than 0.05), and +0.04 +/- 0.11 degrees C (p less than 0.05) 7, 14, and 21 days following the discontinuation of forced swim stress. The mean response did not differ from baseline 28 days following the last session of forced swim stress. The data suggest that in the recovery phase the animals ceased to be sensitive to nicotine. These findings support the hypothesis that a chronic stressor can produce subsensitivity to nicotine. PMID:2068187

  14. Dissection of the Phenotypic and Genotypic Associations With Nicotinic Dependence

    PubMed Central

    Baker, Timothy B.; Grucza, Richard; Wang, Jen C.; Johnson, Eric O.; Breslau, Naomi; Hatsukami, Dorothy; Smith, Stevens S.; Saccone, Nancy; Saccone, Scott; Rice, John P.; Goate, Alison M.; Bierut, Laura J.

    2012-01-01

    Introduction: Strong evidence demonstrates that nicotine dependence is associated with 4 genetic variants rs16969968, rs6474412, rs3733829, and rs1329650 in large-scale Genome-Wide Association Studies. We examined how these identified genetic variants relate to nicotine dependence defined by different categorical and dimensional measures. Methods: Four genetic variants were analyzed in 2,047 subjects of European descent (1,062 cases and 985 controls). Nicotine dependence was assessed with multiple smoking measures, including the Fagerström Test for Nicotine Dependence, the Diagnostic and Statistical Manual for Mental Disorders-IV (DSM-IV) nicotine dependence, the Nicotine Dependence Syndrome Scale, and the Wisconsin Inventory of Smoking Dependence Motives. Single-item measures of cigarettes per day (CPD) and time to first cigarette (TTF) in the morning were also examined. Results: Among the variants, association effect sizes were largest for rs16969968, with measures of craving and heavy smoking, especially cigarettes smoked per day, showing the largest effects. Significant but weaker associations were found for rs6474412 and rs3733729 but not for rs1329650. None of the more comprehensive measures of smoking behaviors yielded stronger genetic associations with these variants than did CPD. Conclusions: CPD is an important simple measure that captures in part the genetic associations of CHRNA5 and nicotine dependence, even when other more comprehensive measures of smoking behaviors are examined. The CHRNA5 gene is associated with heavy compulsive smoking and craving; this should inform the mission to improve the diagnostic validity of DSM-V. PMID:22102629

  15. Nicotine Dependence and Alcohol Problems from Adolescence to Young Adulthood

    PubMed Central

    Dierker, Lisa; Selya, Arielle; Rose, Jennifer; Hedeker, Donald; Mermelstein, Robin

    2016-01-01

    Background Despite the highly replicated relationship between symptoms associated with both alcohol and nicotine, little is known about this association across time and exposure to both drinking and smoking. In the present study, we evaluate if problems associated with alcohol use are related to emerging nicotine dependence symptoms and whether this relationship varies from adolescence to young adulthood, after accounting for both alcohol and nicotine exposure. Methods The sample was drawn from the Social and Emotional Contexts of Adolescent Smoking Patterns Study which measured smoking, nicotine dependence, alcohol use and alcohol related problems over 6 assessment waves spanning 6 years. Analyses were based on repeated assessment of 864 participants reporting some smoking and drinking 30 days prior to individual assessment waves. Mixed-effects regression models were estimated to examine potential time, smoking and/or alcohol varying effects in the association between alcohol problems and nicotine dependence. Findings Inter-individual differences in mean levels of alcohol problems and within subject changes in alcohol problems from adolescence to young adulthood were each significantly associated with nicotine dependence symptoms over and above levels of smoking and drinking behaviour. This association was consistent across both time and increasing levels of smoking and drinking. Conclusions Alcohol related problems are a consistent risk factor for nicotine dependence over and above measures of drinking and smoking and this association can be demonstrated from the earliest experiences with smoking in adolescents, through the establishment of more regular smoking patterns across the transition to young adulthood. These findings add to accumulating evidence suggesting that smoking and drinking may be related through a mechanism that cannot be wholly accounted for by exposure to either substance. PMID:27610424

  16. Inflammatory Response to Burn Trauma: Nicotine Attenuates Proinflammatory Cytokine Levels

    PubMed Central

    Papst, S.; Reimers, K.; Stukenborg-Colsman, C.; Steinstraesser, L.; Vogt, P. M.; Kraft, T.; Niederbichler, A. D.

    2014-01-01

    Objective: The immune response to an inflammatory stimulus is balanced and orchestrated by stimulatory and inhibitory factors. After a thermal trauma, this balance is disturbed and an excessive immune reaction with increased production and release of proinflammatory cytokines results. The nicotine-stimulated anti-inflammatory reflex offsets this. The goal of this study was to verify that transdermal administration of nicotine downregulates proinflammatory cytokine release after burn trauma. Methods: A 30% total body surface area full-thickness rat burn model was used in Sprague Dawley rats (n = 35, male). The experimental animals were divided into a control group, a burn trauma group, a burn trauma group with additional nicotine treatment, and a sham + nicotine group with 5 experimental animals per group. The last 2 groups received a transdermal nicotine administration of 1.75 mg. The concentrations of tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 were determined in homogenates of hearts, livers, and spleens 12 or 24 hours after burn trauma. Results: Experimental burn trauma resulted in a significant increase in cytokine levels in hearts, livers, and spleens. Nicotine treatment led to a decrease of the effect of the burn trauma with significantly lower concentrations of tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 compared to the trauma group. Conclusions: This study confirms in a standardized burn model that stimulation of the nicotinic acetylcholine receptor is involved in the regulation of effectory molecules of the immune response. Looking at the results of our study, further experiments designed to explore and evaluate the potency and mechanisms of the immunomodulating effects of this receptor system are warranted. PMID:25671045

  17. Role of α4- and α6-containing nicotinic receptors in the acquisition and maintenance of nicotine self-administration.

    PubMed

    Madsen, Heather B; Koghar, Harcharan S; Pooters, Tine; Massalas, Jim S; Drago, John; Lawrence, Andrew J

    2015-05-01

    Tobacco smoking is a major cause of death and disease and as such there is a critical need for the development of new therapeutic approaches to treat nicotine addiction. Here, we utilize genetic and pharmacological tools to further investigate the nicotinic acetylcholine receptor (nAChR) subtypes that support intravenous self-administration of nicotine. α4-S248F mice contain a point mutation within the α4 nAChR subunit which confers increased sensitivity to nicotine and resistance to mecamylamine. Here, we show that acute administration of mecamylamine (2 mg/kg, i.p.) reduces established nicotine self-administration (0.05 mg/kg/infusion) in wild-type (WT), but not in α4-S248F heterozygous mice, demonstrating a role for α4* nAChRs in the modulation of ongoing nicotine self-administration. Administration of N,N-decane-1,10-diyl-bis-3-picolinium diiodide (bPiDI), a selective α6β2* nAChR antagonist, dose dependently (5 and 10 mg/kg, i.p.) impairs the acquisition of nicotine self-administration and reduces established nicotine self-administration in WT mice when administered acutely (10 mg/kg, i.p.). This was not due to a general reduction in locomotor activity and the same dose of bPiDI did not affect operant responding for sucrose. bPiDI treatment (10 mg/kg, i.p.) also impaired both the acquisition and maintenance of nicotine self-administration in α4-S248F heterozygous mice. This provides further evidence for the involvement of α6β2* nAChRs in the reinforcing effects of nicotine that underlies its ability to support ongoing self-administration. Taken together, selective targeting of α6β2* or α4α6β2* nAChRs may prove to be an effective strategy for the development of smoking cessation therapies. PMID:24750355

  18. [Stress-protective properties of lithium nicotinate--a new derivative of nicotinic acid].

    PubMed

    Kresiun, V I

    1984-03-01

    Experiments were made to study stress-protective properties of a new psychotropic agent lithium nicotinate developed on the basis of natural metabolites. Prophylactic treatment of the drug given in courses entails an increase in the physical endurance and work fitness, improvement of animals' orientation under stress, facilitating the avoidance behavior. These effects were particularly demonstrable in highly emotional animals. In these animals, stress produced a paralyzing action. According to the electro- and ballisto-cardiography, the drug prevented the stress-induced disorders of cardiovascular function. PMID:6538449

  19. Low-dose nicotine does not promote lung tumors in mouse models

    Cancer.gov

    Experiments in mice show that low levels of exposure to nicotine, equivalent to those in humans who use nicotine replacement therapy (NRT) to help them quit smoking, did not promote lung tumor growth.

  20. COMPARISON OF WEEKLY EXPOSURES TO ANATOXIN-A AND NICOTINE ON THE MOTOR ACTIVITY OF RATS.

    EPA Science Inventory

    Anatoxin-a is a nicotinic cholinergic agonist that is produced by several genera of cyanobacteria, and has been implicated in several poisoning episodes of wildlife, livestock, domestic animals and people. Previous research on nicotine has obtained tolerance and sensitization ...

  1. Voluntary co-consumption of alcohol and nicotine: Effects of abstinence, intermittency, and withdrawal in mice.

    PubMed

    O'Rourke, Kyu Y; Touchette, Jillienne C; Hartell, Elizabeth C; Bade, Elizabeth J; Lee, Anna M

    2016-10-01

    Alcohol and nicotine are often used together, and there is a high rate of co-occurrence between alcohol and nicotine addiction. Most animal models studying alcohol and nicotine interactions have utilized passive drug administration, which may not be relevant to human co-addiction. In addition, the interactions between alcohol and nicotine in female animals have been understudied, as most studies have used male animals. To address these issues, we developed models of alcohol and nicotine co-consumption in male and female mice that utilized voluntary, oral consumption of unsweetened alcohol, nicotine and water. We first examined drug consumption and preference in single-drug, sequential alcohol and nicotine consumption tests in male and female C57BL/6 and DBA/2J mice. We then tested chronic continuous and intermittent access alcohol and nicotine co-consumption procedures. We found that male and female C57BL/6 mice readily co-consumed unsweetened alcohol and nicotine. In our continuous co-consumption procedures, we found that varying the available nicotine concentration during an alcohol abstinence period affected compensatory nicotine consumption during alcohol abstinence, and affected rebound alcohol consumption when alcohol was re-introduced. Consumption of alcohol and nicotine in an intermittent co-consumption procedure produced higher alcohol consumption levels, but not nicotine consumption levels, compared with the continuous co-consumption procedures. Finally, we found that intermittent alcohol and nicotine co-consumption resulted in physical dependence. Our data show that these voluntary co-consumption procedures can be easily performed in mice and can be used to study behavioral interactions between alcohol and nicotine consumption, which may better model human alcohol and nicotine co-addiction. PMID:27342124

  2. Nicotine is Chemotactic for Neutrophils and Enhances Neutrophil Responsiveness to Chemotactic Peptides

    NASA Astrophysics Data System (ADS)

    Totti, Noel; McCusker, Kevin T.; Campbell, Edward J.; Griffin, Gail L.; Senior, Robert M.

    1984-01-01

    Neutrophils contribute to chronic bronchitis and pulmonary emphysema associated with cigarette smoking. Nicotine was found to be chemotactic for human neutrophils but not monocytes, with a peak activity at ~ 31 micromolar. In lower concentrations (comparable to those in smokers' plasma), nicotine enhanced the response of neutrophils to two chemotactic peptides. In contrast to most other chemoattractants for neutrophils, however, nicotine did not affect degranulation or superoxide production. Nicotine thus may promote inflammation and consequent lung injury in smokers.

  3. Compensatory nicotine self-administration in rats during reduced access to nicotine: an animal model of smoking reduction.

    PubMed

    Harris, Andrew C; Burroughs, Danielle; Pentel, Paul R; LeSage, Mark G

    2008-02-01

    The ability of smoking reduction (e.g., decreasing cigarettes per day) to produce significant reductions in toxin exposure is limited by compensatory increases in smoking behavior. Characterizing factors contributing to the marked individual variability in compensation may be useful for understanding this phenomenon. The goal of the current study was to develop an animal model of smoking reduction and to begin to examine potential behavioral and pharmacokinetic contributors to compensation. Rats trained for nicotine self-administration (NSA) in unlimited access sessions were exposed to a progressive decrease in duration of access to nicotine from 23-hr/day to 10-, 6-, and 2-hr/day. Following a return to 23 hr/day access and extinction, single-dose nicotine pharmacokinetic parameters were determined. Rats exhibited a reduction in total daily nicotine intake during reduced access to NSA, but decreases in nicotine intake were not proportional to decreases in access duration. Compensatory increases in hourly infusion rate were also observed when access was decreased. The magnitude of compensation differed considerably among animals. Early session infusion rate during baseline was significantly correlated, while nicotine clearance was moderately correlated, with 1 measure of compensation. Infusion rates were transiently increased compared to prereduction levels when unlimited access was restored, and this effect was greatest in animals that had exhibited the greatest levels of compensation. These findings indicate that rats exhibit compensatory increases in NSA during reduced access to nicotine, with substantial individual variability. This model may be useful for characterizing underlying factors and potential consequences of compensatory smoking. PMID:18266555

  4. Cannabinoid Receptor 1 Gene Association With Nicotine Dependence

    PubMed Central

    Chen, Xiangning; Williamson, Vernell S.; An, Seon-Sook; Hettema, John M.; Aggen, Steven H.; Neale, Michael C.; Kendler, Kenneth S.

    2009-01-01

    Context The endogenous cannabinoid system has been implicated in drug addiction in animal models. The cannabinoid receptor 1 (CNR1) gene is 1 of the 2 receptors expressed in the brain. It has been reported to be associated with alcoholism and multiple drug abuse and dependence. Objective To test the hypothesis that the CNR1 gene is associated with nicotine dependence. Design Genotype-phenotype association study. Ten single-nucleotide polymorphisms were genotyped in the CNR1 gene in 2 independent samples. For the first sample (n=688), a 3-group case-control design was used to test allele association with smoking initiation and nicotine dependence. For the second sample (n = 961), association was assessed with scores from the Fagerström Test for Nicotine Dependence (FTND). Settings Population samples selected from the Mid-Atlantic Twin Registry. Participants White patients aged 18 to 65 years who met the criteria of inclusion. Main Outcome Measures Fagerström Tolerance Questionnaire and FTND scores. Results Significant single-marker and haplotype associations were found in both samples, and the associations were female specific. Haplotype 1-1-2 of markers rs2023239-rs12720071-rs806368 was associated with nicotine dependence and FTND score in the 2 samples (P<.001 and P = .009, respectively). Conclusion Variants and haplotypes in the CNR1 gene may alter the risk for nicotine dependence, and the associations are likely sex specific. PMID:18606954

  5. Diacylglycerol lipase disinhibits VTA dopamine neurons during chronic nicotine exposure

    PubMed Central

    Buczynski, Matthew W.; Herman, Melissa A.; Natividad, Luis A.; Irimia, Cristina; Polis, Ilham Y.; Pugh, Holly; Chang, Jae Won; Niphakis, Micah J.; Cravatt, Benjamin F.; Roberto, Marisa; Parsons, Loren H.

    2016-01-01

    Chronic nicotine exposure (CNE) alters synaptic transmission in the ventral tegmental area (VTA) in a manner that enhances dopaminergic signaling and promotes nicotine use. The present experiments identify a correlation between enhanced production of the endogenous cannabinoid 2-arachidonoylglycerol (2-AG) and diminished release of the inhibitory neurotransmitter GABA in the VTA following CNE. To study the functional role of on-demand 2-AG signaling in GABAergic synapses, we used 1,2,3-triazole urea compounds to selectively inhibit 2-AG biosynthesis by diacylglycerol lipase (DAGL). The potency and selectivity of these inhibitors were established in rats in vitro (rat brain proteome), ex vivo (brain slices), and in vivo (intracerebroventricular administration) using activity-based protein profiling and targeted metabolomics analyses. Inhibition of DAGL (2-AG biosynthesis) rescues nicotine-induced VTA GABA signaling following CNE. Conversely, enhancement of 2-AG signaling in naïve rats by inhibiting 2-AG degradation recapitulates the loss of nicotine-induced GABA signaling evident following CNE. DAGL inhibition reduces nicotine self-administration without disrupting operant responding for a nondrug reinforcer or motor activity. Collectively, these findings provide a detailed characterization of selective inhibitors of rat brain DAGL and demonstrate that excessive 2-AG signaling contributes to a loss of inhibitory GABAergic constraint of VTA excitability following CNE. PMID:26755579

  6. Clarifying the Relationship between Impulsive Delay Discounting and Nicotine Dependence

    PubMed Central

    Amlung, Michael; MacKillop, James

    2014-01-01

    Impulsive delayed reward discounting (DRD) has been linked to nicotine dependence, but with some inconsistency. This may be related to the considerable variability in the literature with regard to the DRD assessments used, particularly in the case of reward magnitudes assessed. In addition, previous studies have often not considered concurrent substance use when examining the relationship between DRD and nicotine dependence. The current study sought to further clarify the relationship between DRD and nicotine dependence by characterizing DRD across diverse reward magnitudes and incorporating other substance use. Daily smokers (N = 933) were assessed for DRD preferences across nine reward magnitudes (delayed reward range: $2.50–$850), comorbid substance use, and relevant demographic variables (age, education, income). A significant large effect size magnitude effect was found for DRD, reflecting steeper discounting for smaller delayed rewards, but significant correlations across magnitudes also suggested similar relative levels of discounting. Principal components analysis (PCA) was used to generate a single latent index of discounting across all magnitudes that accounted for 67% of the total variance. In both correlation and regression analyses, steeper composite DRD was significantly associated with nicotine dependence severity. This relationship remained statistically significant after incorporating demographic variables and alcohol and illicit drug use. These findings provide evidence of a specific link between impulsive DRD and nicotine dependence, and reveal that this association is robust across a broad range of monetary rewards. The study also demonstrates the utility of using PCA to generate latent indices of delay discounting across multiple magnitudes of delayed reward. PMID:24841186

  7. A Systematic Analysis of Candidate Genes Associated with Nicotine Addiction

    PubMed Central

    Liu, Meng; Li, Xia; Fan, Rui; Liu, Xinhua; Wang, Ju

    2015-01-01

    Nicotine, as the major psychoactive component of tobacco, has broad physiological effects within the central nervous system, but our understanding of the molecular mechanism underlying its neuronal effects remains incomplete. In this study, we performed a systematic analysis on a set of nicotine addiction-related genes to explore their characteristics at network levels. We found that NAGenes tended to have a more moderate degree and weaker clustering coefficient and to be less central in the network compared to alcohol addiction-related genes or cancer genes. Further, clustering of these genes resulted in six clusters with themes in synaptic transmission, signal transduction, metabolic process, and apoptosis, which provided an intuitional view on the major molecular functions of the genes. Moreover, functional enrichment analysis revealed that neurodevelopment, neurotransmission activity, and metabolism related biological processes were involved in nicotine addiction. In summary, by analyzing the overall characteristics of the nicotine addiction related genes, this study provided valuable information for understanding the molecular mechanisms underlying nicotine addiction. PMID:26097843

  8. Nicotinic modulation of intrinsic brain networks in schizophrenia

    PubMed Central

    Smucny, Jason; Tregellas, Jason

    2014-01-01

    The nicotinic receptor is a promising drug target currently being investigated for the treatment of cognitive symptoms in schizophrenia. A key step in this process is the development of noninvasive functional neuroimaging biomarkers that can be used to determine if nicotinic agents are eliciting their targeted biological effect, ideally through modulation of a fundamental aspect of neuronal function. To that end, neuroimaging researchers are beginning to understand how nicotinic modulation affects “intrinsic” brain networks to elicit potentially therapeutic effects. An intrinsic network is a functionally and (often) structurally connected network of brain areas whose activity reflects a fundamental neurobiological organizational principle of the brain. This review summarizes findings of the effects of nicotinic drugs on three topics related to intrinsic brain network activity: (1) the default mode network, a group of brain areas for which activity is maximal at rest and reduced during cognitive tasks, (2) the salience network, which integrates incoming sensory data with prior internal representations to guide future actions and change predictive values, and (3) multi-scale complex network dynamics, which describe these brain’s ability to efficiency integrate information while preserving local functional specialization. These early findings can be used to inform future neuroimaging studies that examine the network effects of nicotinic agents. PMID:23796751

  9. Clarifying the relationship between impulsive delay discounting and nicotine dependence.

    PubMed

    Amlung, Michael; MacKillop, James

    2014-09-01

    Impulsive delayed reward discounting (DRD) has been linked to nicotine dependence, but with some inconsistency. This may be related to the considerable variability in the literature with regard to the DRD assessments used, particularly in the case of the reward magnitudes assessed. In addition, previous studies have often not considered concurrent substance use when examining the relationship between DRD and nicotine dependence. The current study sought to further clarify the relationship between DRD and nicotine dependence by characterizing DRD across diverse reward magnitudes and incorporating other substance use. Daily smokers (N = 933) were assessed for DRD preferences across nine reward magnitudes (delayed reward range: $2.50-$850), comorbid substance use, and relevant demographic variables (age, education, income). A significant large effect size magnitude effect was found for DRD, reflecting steeper discounting for smaller delayed rewards, but significant correlations across magnitudes also suggested similar relative levels of discounting. Principal components analysis (PCA) was used to generate a single latent index of discounting across all magnitudes that accounted for 69% of the total variance. In correlation and regression analyses, steeper composite DRD was significantly associated with nicotine dependence severity. This relationship remained statistically significant after incorporating demographic variables and alcohol and illicit drug use. These findings provide evidence of a specific link between impulsive DRD and nicotine dependence and reveal that this association is robust across a broad range of monetary rewards. The study also demonstrates the utility of using PCA to generate latent indices of delay discounting across multiple magnitudes of delayed reward. PMID:24841186

  10. Impaired Lung Mitochondrial Respiration Following Perinatal Nicotine Exposure in Rats.

    PubMed

    Cannon, Daniel T; Liu, Jie; Sakurai, Reiko; Rossiter, Harry B; Rehan, Virender K

    2016-04-01

    Perinatal smoke/nicotine exposure predisposes to chronic lung disease and morbidity. Mitochondrial abnormalities may contribute as the PPARγ pathway is involved in structural and functional airway deficits after perinatal nicotine exposure. We hypothesized perinatal nicotine exposure results in lung mitochondrial dysfunction that can be rescued by rosiglitazone (RGZ; PPARγ receptor agonist). Sprague-Dawley dams received placebo (CON), nicotine (NIC, 1 mg kg(-1)), or NIC + RGZ (3 mg kg(-1)) daily from embryonic day 6 to postnatal day 21. Parenchymal lung (~10 mg) was taken from adult male offspring for mitochondrial assessment in situ. ADP-stimulated O2 consumption was less in NIC and NIC + RGZ compared to CON (F[2,14] = 17.8; 4.5 ± 0.8 and 4.1 ± 1.4 vs. 8.8 ± 2.5 pmol s mg(-1); p < 0.05). The respiratory control ratio for ADP, an index of mitochondrial coupling, was reduced in NIC and remediated in NIC + RGZ (F[2,14] = 3.8; p < 0.05). Reduced mitochondrial oxidative capacity and abnormal coupling were evident after perinatal nicotine exposure. RGZ improved mitochondrial function through tighter coupling of oxidative phosphorylation. PMID:26899624

  11. Nicotine Acutely Inhibits Erectile Tumescence by Altering Heart Rate Variability

    PubMed Central

    Harte, Christopher B.

    2014-01-01

    Objective To examine potential mechanisms underlying nicotine’s effects on male sexual arousal by exploring the mediating role of heart rate variability (HRV). Methods The sample comprised 22 healthy, nicotine-naïve men (Mage = 20.91 years; SD = 2.43). Data were taken from a double-blind, randomized, placebo-controlled, crossover trial previously completed and published elsewhere. During each laboratory visit, time-domain parameters of HRV (standard deviation of normal-to-normal [NN] intervals [SDNN], square root of the mean squared difference of successive NN intervals [RMSSD], percent of NN intervals for which successive heartbeat intervals differed by at least 50 ms [pNN50]) were assessed, as well as objective (via penile plethysmography) and subjective indices of sexual arousal. Results Acute nicotine ingestion (compared to placebo) was associated with dysregulated sympathovagal balance, which in turn was related to relatively reduced erectile tumescence. HRV did not mediate relations between nicotine intake and self-reported indices of sexual arousal. Conclusions HRV mediated the association between nicotine ingestion and erectile capacity. Findings suggest that dysfunctional cardiac autonomic tone may be an underlying mechanism by which nicotine exerts its deleterious effects on erectile health. PMID:24642073

  12. Craving and nicotine withdrawal in a Spanish smoking cessation sample.

    PubMed

    Piñeiro, Bárbara; López-Durán, Ana; Fernández del Río, Elena; Martínez, Úrsula; Brandon, Thomas H; Becoña, Elisardo

    2014-01-01

    Craving and nicotine withdrawal syndrome (NWS) are components of the tobacco use disorder in DSM-5. They both appear after smoking cessation or an abrupt reduction in tobacco use, and they are associated with both short and long-term smoking-cessation outcomes. The aim of the present study was to examine the association of craving and withdrawal with smoking cessation at the end of the treatment and relapse at 3 months follow-up in a Spanish sample of smokers. The sample comprised 342 smokers (37.7% men; 62.3% women) receiving a cognitive-behavioral treatment for smoking cessation. The assessments of craving and withdrawal were conducted using the Minnesota Nicotine Withdrawal Scale. Abstainers at the end of the treatment, compared to non abstainers, showed significantly lower post-treatment withdrawal, and post-treatment craving. Furthermore, they had lower scores in pre-treatment nicotine dependence. Among abstainers, craving decreased significantly from pre-cessation levels, while in those participants who did not quit smoking it remained on the same levels. High nicotine dependence was a predictor of smoking at the end of the treatment, whereas high nicotine withdrawal predicted relapse at 3 months. Findings support the robust role of craving and NWS in smoking cessation and relapse, although they differ in their specific patterns of change over time. PMID:25314038

  13. A Systematic Analysis of Candidate Genes Associated with Nicotine Addiction.

    PubMed

    Liu, Meng; Li, Xia; Fan, Rui; Liu, Xinhua; Wang, Ju

    2015-01-01

    Nicotine, as the major psychoactive component of tobacco, has broad physiological effects within the central nervous system, but our understanding of the molecular mechanism underlying its neuronal effects remains incomplete. In this study, we performed a systematic analysis on a set of nicotine addiction-related genes to explore their characteristics at network levels. We found that NAGenes tended to have a more moderate degree and weaker clustering coefficient and to be less central in the network compared to alcohol addiction-related genes or cancer genes. Further, clustering of these genes resulted in six clusters with themes in synaptic transmission, signal transduction, metabolic process, and apoptosis, which provided an intuitional view on the major molecular functions of the genes. Moreover, functional enrichment analysis revealed that neurodevelopment, neurotransmission activity, and metabolism related biological processes were involved in nicotine addiction. In summary, by analyzing the overall characteristics of the nicotine addiction related genes, this study provided valuable information for understanding the molecular mechanisms underlying nicotine addiction. PMID:26097843

  14. Comparison of the behavioral effects of cigarette smoke and pure nicotine in rats

    PubMed Central

    Harris, Andrew C.; Mattson, Christina; LeSage, Mark G.; Keyler, Daniel E.; Pentel, Paul R.

    2010-01-01

    Animal models of tobacco dependence typically rely on parenteral administration of pure nicotine. Models using cigarette smoke inhalation might more accurately simulate nicotine exposure in smokers. The primary goal of this study was to validate methods for administering cigarette smoke to rats using exposure conditions that were clinically relevant and also produced brain nicotine levels similar to those produced by behaviorally active doses of pure nicotine. A secondary goal was to begin examining the behavioral effects of smoke. Nose-only exposure (NOE) to smoke for 10–45 min or whole-body exposure (WBE) to smoke for 1–4 hr produced serum nicotine concentrations similar to those in smokers (14–55 ng/ml), without excessive carbon monoxide exposure. Daily nicotine (0.1 mg/kg, s.c.) induced locomotor sensitization whereas 45-min NOE producing brain nicotine levels within the same range did not. Nicotine 0.125 mg/kg s.c. reversed withdrawal from a chronic nicotine infusion as measured by elevations in intracranial self-stimulation thresholds whereas 4-hr WBE producing similar brain nicotine levels did not. These data demonstrate the feasibility of delivering cigarette smoke to rats at clinically relevant doses, and provide preliminary evidence that the behavioral effects of nicotine delivered in smoke may differ from those of pure nicotine. PMID:20494826

  15. Nicotine Concentrations in Electronic Cigarette Refill and Do-It-Yourself Fluids

    PubMed Central

    Davis, Barbara; Dang, Michael; Kim, Jisoo

    2015-01-01

    Introduction: We evaluated the accuracy of nicotine concentration labeling on electronic cigarette refill products. Methods: The nicotine concentration of 71 electronic cigarette refill fluid products and 1 related do-it-yourself (DIY) product was quantified using high-performance liquid chromatography. Quantified data were compared with manufacturers labeled concentrations. Duplicate refill fluid products purchased at different times were evaluated by visual comparison of fluid coloration and quantified nicotine concentration. Results: Thirty-five of the 54 nicotine-containing fluids had quantified nicotine concentrations that deviated by more than ±10% from the manufacturer labels, with 46 of 50 being in excess of labeled values. Refill fluids labeled as 0 nicotine had no detectable nicotine. Of the 5 products that were unlabeled for nicotine concentration, 3 contained no detectable nicotine, whereas the remaining 2 contained nicotine in excess of 100mg/ml and may have been intended for DIY use. Sixteen of the 18 duplicate bottles of refill fluid varied greatly in their nicotine concentrations. One of the 5 companies showed significant improvement in labeling accuracy among the most recently purchased products. Of the 23 total duplicate pairs, 15 of 23 varied in coloration from their mates. Conclusions: Nicotine concentration labeling on electronic cigarette refill products was often inaccurate but showed improvement recently in products from 1 company. To ensure the safety of refill fluids and DIY products, it is necessary to establish quality control guidelines for the manufacturing and labeling and to monitor products longitudinally. PMID:24862971

  16. ENVIRONMENTAL TOBACCO SMOKE EXPOSURE OF YOUNG CHILDREN AS ASSESSED USING A PASSIVE DIFFUSION DEVICE FOR NICOTINE

    EPA Science Inventory

    Indoor air nicotine concentrations in the homes of young children (ages 1-3) were monitored for 48 hours as part of a study to assess uptake, metabolism and urinary excretion of nicotine and its metabolites including cotinine. otinine, a metabolite of nicotine, has been used as a...

  17. Nicotine induces mitochondrial fission through mitofusin degradation in human multipotent embryonic carcinoma cells.

    PubMed

    Hirata, Naoya; Yamada, Shigeru; Asanagi, Miki; Sekino, Yuko; Kanda, Yasunari

    2016-02-01

    Nicotine is considered to contribute to the health risks associated with cigarette smoking. Nicotine exerts its cellular functions by acting on nicotinic acetylcholine receptors (nAChRs), and adversely affects normal embryonic development. However, nicotine toxicity has not been elucidated in human embryonic stage. In the present study, we examined the cytotoxic effects of nicotine in human multipotent embryonal carcinoma cell line NT2/D1. We found that exposure to 10 μM nicotine decreased intracellular ATP levels and inhibited proliferation of NT2/D1 cells. Because nicotine suppressed energy production, which is a critical mitochondrial function, we further assessed the effects of nicotine on mitochondrial dynamics. Staining with MitoTracker revealed that 10 μM nicotine induced mitochondrial fragmentation. The levels of the mitochondrial fusion proteins, mitofusins 1 and 2, were also reduced in cells exposed to nicotine. These nicotine effects were blocked by treatment with mecamylamine, a nonselective nAChR antagonist. These data suggest that nicotine degrades mitofusin in NT2/D1 cells and thus induces mitochondrial dysfunction and cell growth inhibition in a nAChR-dependent manner. Thus, mitochondrial function in embryonic cells could be used to assess the developmental toxicity of chemicals. PMID:26774337

  18. Effect of nicotine on melanogenesis and antioxidant status in HEMn-LP melanocytes

    SciTech Connect

    Delijewski, Marcin; Beberok, Artur; Otręba, Michał; Wrześniok, Dorota; Rok, Jakub; Buszman, Ewa

    2014-10-15

    Nicotine is a natural ingredient of tobacco plants and is responsible for the addictive properties of tobacco. Nowadays nicotine is also commonly used as a form of smoking cessation therapy. It is suggested that nicotine may be accumulated in human tissues containing melanin. This may in turn affect biochemical processes in human cells producing melanin. The aim of this study was to examine the effect of nicotine on melanogenesis and antioxidant status in cultured normal human melanocytes HEMn-LP. Nicotine induced concentration-dependent loss in melanocytes viability. The value of EC{sub 50} was determined to be 7.43 mM. Nicotine inhibited a melanization process in human light pigmented melanocytes and caused alterations of antioxidant defense system. Significant changes in cellular antioxidant enzymes: superoxide dismutase and catalase activities and in hydrogen peroxide content were stated. The obtained results may explain a potential influence of nicotine on biochemical processes in melanocytes in vivo during long term exposition to nicotine. - Graphical abstract: Nicotine inhibits melanogenesis and induces oxidative stress in HEMn-LP melanocytes. - Highlights: • Nicotine induces concentration-dependent loss in melanocytes viability. • Nicotine in non-cytotoxic concentrations inhibits melanogenesis. • Nicotine in higher concentrations induces oxidative stress.

  19. Shed king cobra and cobra skins as model membranes for in-vitro nicotine permeation studies.

    PubMed

    Pongjanyakul, Thaned; Prakongpan, Sompol; Panomsuk, Suwannee; Puttipipatkhachorn, Satit; Priprem, Aroonsri

    2002-10-01

    Shed king cobra skin (SKCS) and shed cobra skin (SCS) were investigated for use as barrier membranes, including some pre-hydration factors, for in-vitro nicotine permeation. Inter-specimen variations in nicotine fluxes using shed snake skin were compared with those using human epidermis. Nicotine in the form of 1% w/v aqueous buffer solution at pH 5 and transdermal patches (dose 14 mg day(-1)) were used. The nicotine fluxes across the shed snake skin were not significantly affected (P > 0.05) by temperature and duration of hydration pre-treatment. Scanning electron micrographs of SKCS and SCS revealed a remarkable difference in surface morphology, but the nicotine fluxes using both shed skins were not significantly different (P > 0.05). When compared with the results obtained using human epidermis, there were similarities in fluxes and permeation profiles of nicotine. Using nicotine solution, the nicotine permeation profiles of all membranes followed zero order kinetics. The amount of nicotine permeated provided good linearity with the square root of time over 24 h (R(2) > 0.98) when using nicotine patches. The nicotine fluxes using SKCS and SCS had less inter-specimen variation than those using human epidermis. The results suggest a potential use for SKCS or SCS as barrier membranes for in-vitro nicotine permeation studies. PMID:12396295

  20. Comorbidity of Psychiatric Disorders and Nicotine Dependence among Adolescents: Findings from a Prospective, Longitudinal Study

    ERIC Educational Resources Information Center

    Griesler, Pamela C.; Hu, Mei-Chen; Schaffram, Christine; Kandel, Denise B.

    2008-01-01

    The relationship between nicotine dependence and DSM-IV psychiatric disorders in 1,039 adolescents is examined. Findings revealed that psychiatric disorders most usually predicted the onset of the first basis of nicotine dependence while nicotine dependence does not appear to have an influence on the onset of psychiatric disorders. Other…

  1. Developmental Neurotoxicity of Tobacco Smoke Directed Toward Cholinergic and Serotonergic Systems: More Than Just Nicotine.

    PubMed

    Slotkin, Theodore A; Skavicus, Samantha; Card, Jennifer; Stadler, Ashley; Levin, Edward D; Seidler, Frederic J

    2015-09-01

    Tobacco smoke contains thousands of compounds in addition to nicotine, a known neuroteratogen. We evaluated the developmental neurotoxicity of tobacco smoke extract (TSE) administered to pregnant rats starting preconception and continued through the second postnatal week. We simulated nicotine concentrations encountered with second-hand smoke, an order of magnitude below those seen in active smokers, and compared TSE with an equivalent dose of nicotine alone, and to a 10-fold higher nicotine dose. We conducted longitudinal evaluations in multiple brain regions, starting in adolescence (postnatal day 30) and continued to full adulthood (day 150). TSE exposure impaired presynaptic cholinergic activity, exacerbated by a decrement in nicotinic cholinergic receptor concentrations. Although both nicotine doses produced presynaptic cholinergic deficits, these were partially compensated by hyperinnervation and receptor upregulation, effects that were absent with TSE. TSE also produced deficits in serotonin receptors in females that were not seen with nicotine. Regression analysis showed a profound sex difference in the degree to which nicotine could account for overall TSE effects: whereas the 2 nicotine doses accounted for 36%-46% of TSE effects in males, it accounted for only 7%-13% in females. Our results show that the adverse effects of TSE on neurodevelopment exceed those that can be attributed to just the nicotine present in the mixture, and further, that the sensitivity extends down to levels commensurate with second-hand smoke exposure. Because nicotine itself evoked deficits at low exposures, "harm reduction" nicotine products do not eliminate the potential for neurodevelopmental damage. PMID:26085346

  2. [Pharmacology of niacin or nicotinic acid].

    PubMed

    Santos, Raul D

    2005-10-01

    Niacin or nicotinic acid is a soluble vitamin with hypolipidemic properties. Niacin reduces triglycerides (20 50%), LDL-c (5-25%), and raises HDL-c (15-35%). The Coronary Drug Project study showed that the use of niacin was associated with reduction on coronary events and total mortality, and more recently it has been demonstrated that niacin combined with other hypolipidemic drugs can attenuate the progression of coronary atherosclerosis. Niacin appears to reduce the mobilization of free fatty acids from the adipocytes, acting on specific receptors, diminishing the liver formation of triglyceride-rich lipoproteins. There are two forms of niacin, one of rapid absorption (crystalline), more commonly associated with flushing, and another of extended release, recently reported to be better tolerated. The use of niacin can be associated with dyspepsia, increased plasma levels of liver enzymes and also with a modest elevation in glucose and uric acid plasma levels, at least using the extended-release preparation up to 2 g/d. PMID:16400392

  3. Does nicotinic acid (niacin) lower blood pressure?

    PubMed

    Bays, H E; Rader, D J

    2009-01-01

    Nicotinic acid (niacin) is a well-established treatment for dyslipidaemia - an important cardiovascular disease (CVD) risk factor. However, niacin may also reduce blood pressure (BP), which is another important CVD risk factor. This review examines the limited publicly available data on niacin's BP effects. Acute administration of immediate-release niacin may lower BP because of niacin's acute vasodilatory effects. Although not always supported by clinical trial data, the package insert of a prescription, extended-release niacin describes niacin-induced acute hypotension. From a chronic standpoint, larger studies, such as the Coronary Drug Project, suggest that niacin may lower BP when administered over a longer period of time. Post hoc analyses of some of the more recent niacin clinical trials also support a more chronic, dose-dependent, BP-lowering effect of niacin. Because laropiprant [a prostaglandin D(2) (PGD(2)) type 1 (DP1) receptor antagonist] does not attenuate niacin's BP-lowering effects, it is unlikely that any chronic lowering of BP by niacin is due to dilation of dermal vessels through activation of the DP1 receptor by PGD(2.) Further research is warranted to evaluate the extent and mechanisms of niacin's effects on BP. PMID:19054161

  4. Genetic Relationship between Schizophrenia and Nicotine Dependence.

    PubMed

    Chen, Jingchun; Bacanu, Silviu-Alin; Yu, Hui; Zhao, Zhongming; Jia, Peilin; Kendler, Kenneth S; Kranzler, Henry R; Gelernter, Joel; Farrer, Lindsay; Minica, Camelia; Pool, Rene; Milaneschi, Yuri; Boomsma, Dorret I; Penninx, Brenda W J H; Tyndale, Rachel F; Ware, Jennifer J; Vink, Jacqueline M; Kaprio, Jaakko; Munafò, Marcus; Chen, Xiangning

    2016-01-01

    It is well known that most schizophrenia patients smoke cigarettes. There are different hypotheses postulating the underlying mechanisms of this comorbidity. We used summary statistics from large meta-analyses of plasma cotinine concentration (COT), Fagerström test for nicotine dependence (FTND) and schizophrenia to examine the genetic relationship between these traits. We found that schizophrenia risk scores calculated at P-value thresholds of 5 × 10(-3) and larger predicted FTND and cigarettes smoked per day (CPD), suggesting that genes most significantly associated with schizophrenia were not associated with FTND/CPD, consistent with the self-medication hypothesis. The COT risk scores predicted schizophrenia diagnosis at P-values of 5 × 10(-3) and smaller, implying that genes most significantly associated with COT were associated with schizophrenia. These results implicated that schizophrenia and FTND/CPD/COT shared some genetic liability. Based on this shared liability, we identified multiple long non-coding RNAs and RNA binding protein genes (DA376252, BX089737, LOC101927273, LINC01029, LOC101928622, HY157071, DA902558, RBFOX1 and TINCR), protein modification genes (MANBA, UBE2D3, and RANGAP1) and energy production genes (XYLB, MTRF1 and ENOX1) that were associated with both conditions. Further analyses revealed that these shared genes were enriched in calcium signaling, long-term potentiation and neuroactive ligand-receptor interaction pathways that played a critical role in cognitive functions and neuronal plasticity. PMID:27164557

  5. Genetic Relationship between Schizophrenia and Nicotine Dependence

    PubMed Central

    Chen, Jingchun; Bacanu, Silviu-Alin; Yu, Hui; Zhao, Zhongming; Jia, Peilin; Kendler, Kenneth S.; Kranzler, Henry R.; Gelernter, Joel; Farrer, Lindsay; Minica, Camelia; Pool, Rene; Milaneschi, Yuri; Boomsma, Dorret I.; Penninx, Brenda W. J. H.; Tyndale, Rachel F.; Ware, Jennifer J.; Vink, Jacqueline M.; Kaprio, Jaakko; Munafò, Marcus; Chen, Xiangning; Ware, Jennifer J.; Chen, Xiangning; Vink, Jacqueline M.; Loukola, Anu; Minica, Camelia; Pool, Rene; Milaneschi, Yuri; Mangino, Massimo; Menni, Cristina; Chen, Jingchun; Peterson, Roseann; Auro, Kirsi; Lyytikäinen, Leo-Pekka; Wedenoja, Juho; Stiby, Alex I.; Hemani, Gibran; Willemsen, Gonneke; Hottenga, Jouke Jan; Korhonen, Tellervo; Heliövaara, Markku; Perola, Markus; Rose, Richard; Paternoster, Lavinia; Timpson, Nic; Wassenaar, Catherine A.; Zhu, Andy Z. X.; Smith, George Davey; Raitakari, Olli; Lehtimäki, Terho; Kähönen, Mika; Koskinen, Seppo; Spector, Timothy; Penninx, Brenda W. J. H.; Salomaa, Veikko; Boomsma, Dorret I.; Tyndale, Rachel F.; Kaprio, Jaakko; Munafò, Marcus; Ware, Jennifer J.; Chen, Xiangning; Vink, Jacqueline M.; Loukola, Anu; Minica, Camelia; Chen, Jingchun; Peterson, Roseann; Timpson, Nic; Taylor, Michelle; Boomsma, Dorret I.; Kaprio, Jaakko; Munafò, Marcus; Maes, Hermine; Riley, Brien; Kendler, Kenneth S.; Gelernter, Joel; Sherva, Richard; Farrer, Lindsay; Kranzler, Henry R.; Maher, Brion; Vanyukov, Michael

    2016-01-01

    It is well known that most schizophrenia patients smoke cigarettes. There are different hypotheses postulating the underlying mechanisms of this comorbidity. We used summary statistics from large meta-analyses of plasma cotinine concentration (COT), Fagerström test for nicotine dependence (FTND) and schizophrenia to examine the genetic relationship between these traits. We found that schizophrenia risk scores calculated at P-value thresholds of 5 × 10−3 and larger predicted FTND and cigarettes smoked per day (CPD), suggesting that genes most significantly associated with schizophrenia were not associated with FTND/CPD, consistent with the self-medication hypothesis. The COT risk scores predicted schizophrenia diagnosis at P-values of 5 × 10−3 and smaller, implying that genes most significantly associated with COT were associated with schizophrenia. These results implicated that schizophrenia and FTND/CPD/COT shared some genetic liability. Based on this shared liability, we identified multiple long non-coding RNAs and RNA binding protein genes (DA376252, BX089737, LOC101927273, LINC01029, LOC101928622, HY157071, DA902558, RBFOX1 and TINCR), protein modification genes (MANBA, UBE2D3, and RANGAP1) and energy production genes (XYLB, MTRF1 and ENOX1) that were associated with both conditions. Further analyses revealed that these shared genes were enriched in calcium signaling, long-term potentiation and neuroactive ligand-receptor interaction pathways that played a critical role in cognitive functions and neuronal plasticity. PMID:27164557

  6. SOLID SOLUTION EFFECTS ON THE THERMAL PROPERTIES IN THE MgAl2O4-MgGa2O4

    SciTech Connect

    O'Hara, Kelley; Smith, Jeffrey D; Sander, Todd P.; Hemrick, James Gordon

    2013-01-01

    Solid solution eects on thermal conductivity within the MgO-Al2O3-Ga2O3 system were studied. Samples with systematically varied additions of MgGa2O4 to MgAl2O4 were prepared and the laser ash technique was used to determine thermal diusivity at temperatures between 200C and 1300C. Heat capacity as a function of temperature from room temperature to 800C was also determined using dierential scanning calorimetry. Solid solution in the MgAl2O4-MgGa2O4 system decreases the thermal conductivity up to 1000C. At 200C thermal conductivity decreased 24% with a 5 mol% addition of MgGa2O4 to the system. At 1000C the thermal conductivity decreased 13% with a 5 mol% addition. Steady state calculations showed a 12.5% decrease in heat ux with 5 mol% MgGa2O4 considered across a 12 inch thickness.

  7. Nicotine Effects in Adolescence and Adulthood on Cognition and α4β2-Nicotinic Receptors in the Neonatal Ventral Hippocampal Lesion Rat Model of Schizophrenia

    PubMed Central

    Berg, Sarah A.; Sentir, Alena M.; Bell, Richard L.; Engleman, Eric A.; Chambers, R. Andrew

    2014-01-01

    Rational Nicotine use in schizophrenia has traditionally been explained as ‘self-medication’ of cognitive and/or nicotinic acetylcholinergic receptor (nAChR) abnormalities. Objectives We test this hypothesis in a neurodevelopmental rat model of schizophrenia that shows increased addiction behaviors including enhanced nicotine reinforcement and drug-seeking. Methods Nicotine transdermal patch (5 mg/kg/day vs. placebo × 10 days in adolescence or adulthood) effects on subsequent radial-arm maze learning (15 sessions) and frontal-cortical-striatal nAChR densities (α4β2; [3H]-epibatidine binding) were examined in neonatal ventral hippocampal lesion (NVHL) and SHAM-operated rats. Results NVHL cognitive deficits were not differentially affected by nicotine history compared to SHAMs. Nicotine history produced minimal cognitive effects while increasing food–reward consumption on the maze, compounding with NVHL-induced overconsumption. Acute nicotine (0.5 mg/kg) delivered before the final maze sessions produced modest improvements in maze performance in rats with nicotine patch histories only, but not differentially so in NVHLs. Consistent with in vivo neuroimaging of β2 nAChR binding in schizophrenia smokers vs. non-smokers and healthy controls, adult NVHLs showed 12% reductions in nAChR binding in MPFC (p<0.05) but not ventral striatum (<5% changes, p>.40), whereas nicotine history elevated nAChRs across both regions (>30%, p<0.001) without interacting with NVHLs. Adolescent vs. adult nicotine exposure did not alter nAChRs differentially. Conclusions Although replicating nicotine-induced up-regulation of nAChRs in human smokers and demonstrating NVHL validity in terms of schizophrenia-associated nAChR density patterns, these findings do not support hypotheses explaining increased nicotine use in schizophrenia as reflecting illness-specific effects of nicotine to therapeutically alter cognition or nAChR densities. PMID:25388292

  8. Positive allosteric modulation of α4β2 nicotinic acetylcholine receptors as a new approach to smoking reduction: evidence from a rat model of nicotine self-administration

    PubMed Central

    Liu, Xiu

    2013-01-01

    Rationale The α4β2 subtype of nicotinic acetylcholine receptors (nAChRs) plays a central role in the mediation of nicotine reinforcement. Positive allosteric modulators (PAMs) at α4β2 nAChRs facilitate the intrinsic efficiency of these receptors although they do not directly activate the receptors. α4β2 PAMs are hypothesized to reduce nicotine self-administration in subjects engaged in routine nicotine consumption. The present study tested this hypothesis using a rat model of nicotine self-administration. Methods Male Sprague-Dawley rats were trained in daily 1 h sessions to intravenously self-administer nicotine (0.03 mg/kg/infusion, free base) on a fixed-ratio 5 schedule. Effects of the α4β2 PAM desformylflustrabromine (dFBr), α4β2 agonist 5-iodo-A-85380, and acetylcholinesterase inhibitor galantamine on nicotine intake were examined. The ability of dFBr and 5-iodo-A-85380 to substitute for nicotine was also assessed. Results dFBr and 5-iodo-A-85380 dose-dependently reduced nicotine self-administration without changing lever responses for food. Galantamine decreased self-administration of nicotine and food at high doses. Unlike 5-iodo-A-85380, dFBr failed to substitute for nicotine in supporting self-administration behavior. Conclusions These results demonstrated the effectiveness of dFBr in reducing nicotine intake and the inability of dFBr to support self-administration behavior. These findings suggest that positive allosteric modulation of α4β2 nAChRs may be a promising target for the treatment of nicotine addiction. Moreover, α4β2 PAMs, in contrast to agonist medications, may have clinical advantages because they may have little liability for abuse because of their lack of reinforcing actions on their own. PMID:23712602

  9. CDP-choline attenuates scopolamine induced disruption of prepulse inhibition in rats: involvement of central nicotinic mechanism.

    PubMed

    Uslu, Gulsah; Savci, Vahide; Buyukuysal, Levent R; Goktalay, Gokhan

    2014-05-21

    It has been shown that cholinergic system plays an important role in schizophrenia-associated cognitive deficits, therefore cholinergic drugs are novel targets for the treatment of cognitive deficits seen in schizophrenia. We aimed to test the effects of CDP-choline on sensorimotor gating functioning, which is an important function for the integration of sensory and cognitive information processing and the execution of appropriate motor responses. In this study, prepulse inhibition (PPI) of the acoustic startle reflex was used to test the sensorimotor gating functioning, and the effects of CDP-choline on scopolamine induced PPI disruption were evaluated in rats. Furthermore, the contribution of the cholinergic mechanism in these effects was determined. CDP-choline (75, 250, 500mg/kg) by itself had no effect on the PPI in naïve animals. Scopolamine (0.4mg/kg; s.c.) significantly decreased the PPI levels and intraperitoneal administration of CDP-choline (250mg/kg) attenuated the effects of scopolamine. A non-specific nicotinic receptor antagonist, mecamylamine and an alpha 7 nicotinic receptor (α7-nAChR) antagonist, methyllycaconitine were used to investigate the mechanism underlying the effects of CDP-choline. Mecamylamine (3mg/kg; s.c.), and methyllycaconitine (10μg; i.c.v.) completely blocked the reversal effects of CDP-choline on scopolamine induced disruption of PPI. These results demonstrate that exogenous administration of CDP-choline attenuates scopolamine induced PPI disruption and show that the activation of central α7-nAChR may play a critical role in this effect. PMID:24708927

  10. Association of withdrawal features with nicotine dependence as measured by the Fagerström Test for Nicotine Dependence (FTND)

    PubMed Central

    Ríos-Bedoya, Carlos F.; Snedecor, Sandy M.; Pomerleau, Cynthia S.; Pomerleau, Ovide F.

    2008-01-01

    The aim of this study is to advance our understanding of how nicotine dependence level, defined by the Fagerström Test of Nicotine Dependence (FTND), relates to nicotine withdrawal features. We classified nicotine dependence in two categories, 1) low dependence (LD; FTND <4) and 2) high dependence (HD; FTND ≥4). A sample of 241 smokers was recruited via newspaper ads and public notices. Using a multivariate response model with adjustments for age, sex, age at first cigarette, race, and current or past history of depression, we observed a small to modest statistically robust association between nicotine dependence level and withdrawal features such as, irritation/anger (adjusted relative risk, aRR = 1.2; 95% CI 1.00, 1.3); nervousness (aRR = 1.3; 95% CI 1.1, 1.6); restlessness (aRR = 1.2; 95% CI 1.1, 1.4); difficulty concentrating (aRR = 1.3; 95% CI 1.1, 1.7); and trouble sleeping (aRR = 1.8; 95% CI 1.2, 2.6). Our findings are consistent with the inference that the FTND measures “physiological dependence” and that multidimensional approaches are needed to capture the full range of smoking phenotypology. PMID:18502052

  11. Exploring brief measures of nicotine dependence for epidemiological surveys.

    PubMed

    de Leon, Jose; Diaz, Francisco J; Becoña, Elisardo; Gurpegui, Manuel; Jurado, Dolores; Gonzalez-Pinto, Ana

    2003-10-01

    A score > or = 6 in the Fagerström Test for Nicotine Dependence (FTND), identifying high nicotine dependence, was compared with three briefer classifications: (1) Item 4: heavy smoking (more than 30 cigarettes per day); (2) Item 1: high early smoking (smoking within 30 min of waking up); and (3) a score > or = 4 by combining Items 1 and 4. The FTND scores from 1642 smokers from five samples in the US and Spain were analyzed. Heavy smoking had low sensitivity. High early smoking had low specificity. A score > or = 4 by combining Items 1 and 4 had relatively good sensitivity (94%) and specificity (88%). Researchers needing definition of nicotine dependence briefer than FTND may want to only use Items 1 and 4 of FTND with a cutting score > or = 4. PMID:14512071

  12. THIAMINE AND NICOTINIC ACID: ANAEROBIC GROWTH FACTORS FOR MUCOR ROUXII

    PubMed Central

    Bartnicki-Garcia, S.; Nickerson, Walter J.

    1961-01-01

    Bartnicki-Garcia, S. (Rutgers, the State University, New Brunswick, N. J.), and Walter J. Nickerson. Thiamine and nicotinic acid: Anaerobic growth factors for Mucor rouxii. J. Bacteriol. 82:142–148. 1961.—Mucor rouxii requires preformed thiamine and nicotinic acid for anaerobic growth. Such requirements are not manifested during aerobic incubation. Aerobically, the fungus was shown to be able to synthesize both vitamins. The yeastlike form and the filamentous form of anaerobically grown M. rouxii exhibit the same vitamin requirements. Thiamine can be substituted by its thiazole moiety. Under certain conditions, nicotinic acid was partly substituted by tryptophan, kynurenine, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid. Anaerobically. the fungus (thiamine requiring) was about ten times more susceptible to pyrithiamine antagonism than the same organism grown aerobically (thiamine independent). PMID:16561911

  13. Consumption and foraging behaviors for common stimulants (nicotine, caffeine).

    PubMed

    Phillips, James G; Currie, Jonathan; Ogeil, Rowan P

    2016-01-01

    Models are needed to understand the emerging capability to track consumers' movements. Therefore, we examined the use of legal and readily available stimulants that vary in their addictive potential (nicotine, caffeine). One hundred sixty-six participants answered the Kessler Psychological Distress Scale (K10), the Severity of Dependence Scale for nicotine and caffeine, and reported the number of times and locations stimulants were purchased and used. On average, nicotine dependent individuals made their purchases from 2 locations, while caffeine dependent individuals consumed caffeine at 2 locations, but some people exhibited a greater range and intensity of use. Stimulant foraging behavior could be described by power laws, and is exacerbated by dependency. The finding has implications for attempts to control substance use. PMID:26555360

  14. Determination of nicotine by surface-enhanced Raman scattering (SERS)

    SciTech Connect

    Barber, T.E.; List, M.S.; Haas, J.W. III; Wachter, E.A. )

    1994-11-01

    The analytical application of surface-enhanced Raman spectroscopy (SERS) to the determination of nicotine is demonstrated. A simple spectroelectrochemical method using a copper or silver electrode as the SERS substrate has been developed, consisting of three steps: polishing a working electrode to a mirror finish; roughening the electrode in an electrolyte solution; and, finally, depositing the nicotine analyte onto the roughened electrode after immersion in a sample solution. During the reduction cycle, a large enhancement in nicotine Raman scattering is observed at the electrode surface. The intensity of the SERS signal on a silver electrode is linear with concentration from 10 to 900 ppb, with an estimated detection limit of 7 ppb. The total analysis time per sample is approximately five minutes. This procedure has been used to analyze the extract from a cigarette side-stream smoke sample (environmental tobacco smoke); the SERS results agree well with those of conventional gas chromatographic analysis.

  15. A Two-Day Continuous Nicotine Infusion Is Sufficient to Demonstrate Nicotine Withdrawal in Rats as Measured Using Intracranial Self-Stimulation

    PubMed Central

    Muelken, Peter; Schmidt, Clare E.; Shelley, David; Tally, Laura; Harris, Andrew C.

    2015-01-01

    Avoidance of the negative affective (emotional) symptoms of nicotine withdrawal (e.g., anhedonia, anxiety) contributes to tobacco addiction. Establishing the minimal nicotine exposure conditions required to demonstrate negative affective withdrawal signs in animals, as well as understanding moderators of these conditions, could inform tobacco addiction-related research, treatment, and policy. The goal of this study was to determine the minimal duration of continuous nicotine infusion required to demonstrate nicotine withdrawal in rats as measured by elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior). Administration of the nicotinic acetylcholine receptor antagonist mecamylamine (3.0 mg/kg, s.c.) on alternate test days throughout the course of a 2-week continuous nicotine infusion (3.2 mg/kg/day via osmotic minipump) elicited elevations in ICSS thresholds beginning on the second day of infusion. Magnitude of antagonist-precipitated withdrawal did not change with further nicotine exposure and mecamylamine injections, and was similar to that observed in a positive control group receiving mecamylamine following a 14-day nicotine infusion. Expression of a significant withdrawal effect was delayed in nicotine-infused rats receiving mecamylamine on all test days rather than on alternate test days. In a separate study, rats exhibited a transient increase in ICSS thresholds following cessation of a 2-day continuous nicotine infusion (3.2 mg/kg/day). Magnitude of this spontaneous withdrawal effect was similar to that observed in rats receiving a 9-day nicotine infusion. Our findings demonstrate that rats exhibit antagonist-precipitated and spontaneous nicotine withdrawal following a 2-day continuous nicotine infusion, at least under the experimental conditions studied here. Magnitude of these effects were similar to those observed in traditional models involving more prolonged nicotine exposure. Further development of these models

  16. Adult mice voluntarily progress to nicotine dependence in an oral self-selection assay.

    PubMed

    Locklear, Laura L; McDonald, Craig G; Smith, Robert F; Fryxell, Karl J

    2012-09-01

    Nicotine has both rewarding and aversive properties in rodents, as shown by intravenous self-administration, intracranial self-stimulation, and conditioned place preference experiments. However, high throughput models of nicotine reward have not been developed in mice. In previous two-bottle studies, mice often chose to drink less from the nicotine bottle than from the water bottle, which raises the question whether these paradigms provide a model of the reinforcing properties of oral nicotine. We hypothesized that previous two-bottle choice paradigms included factors (such as the brief duration of trials, the addition of flavorings to both bottles, water bottles located relatively close to each other, etc.) that may have obstructed the formation of a learned association between the taste of nicotine and its delayed pharmacological effects. Here we show that a paradigm designed to simplify the acquisition of a learned association resulted in nicotine consumption by various strains and sexes that diverged progressively over a period of seven weeks. The strain and sex with the highest nicotine consumption (C57BL/6J females) showed steady and statistically significant increases in nicotine consumption throughout this period. C57BL/6J females were clearly responding to the reinforcing properties of nicotine because they chose to drink over 70% of their fluids from the nicotine bottle. Moreover, they became nicotine dependent, as shown by highly significant nicotine withdrawal symptoms after the nicotine bottle was removed. The strain and sex with the lowest consumption (A/J males) showed a significant decrease in nicotine consumption, and by the end of the experiment were drinking only 24% of their fluids from the nicotine bottle. PMID:22583831

  17. The Nicotine Dependence Syndrome Scale in Finnish Smokers

    PubMed Central

    Broms, Ulla; Madden, Pamela A.F.; Heath, Andrew C.; Pergadia, Michele L.; Shiffman, Saul; Kaprio, Jaakko

    2007-01-01

    The Nicotine Dependence Syndrome Scale (NDSS) is a new multidimensional measure of nicotine dependence. The study aim was to examine the structure and heritability of the NDSS and its associations with nicotine dependence defined by FTND and DSM-IV criteria among Finnish smokers participating in an ongoing twin-family study. Adult twin pairs concordant for smoking from the Finnish Twin Cohort Study, and their siblings and parents were interviewed. Among 1370 smokers, the NDSS sum score (a summary measure of dependence) correlated moderately high with FTND score (r=0.62). Subjects in the highest NDSS sum score groups were more likely to be nicotine dependent according to DSM-IV criteria compared with those in the lowest quintile (odds ratio = 36.7, 95% Confidence interval 13.0–103). In exploratory factor analysis we derived three factors, named drive/priority, stereotypy/continuity and tolerance. The drive/priority factor correlated best with FTND (r=0.54). Genetic modelling showed no differences in the genetic architecture of NDSS or FTND by gender; the overall heritability estimate for NDSS was 0.30 (95% CI 0.06–0.47), and for FTND 0.40 (95% CI 0.23–0.55) The NDSS sum score is moderately high associated with DSM-IV nicotine dependence as well as FTND. These analyses indicate that the NDSS functions well in a Finnish family-based sample and provide additional validation of a new scale developed to capture complex behavioral features of nicotine dependence. PMID:17174039

  18. Development of the PROMIS® Nicotine Dependence Item Banks

    PubMed Central

    Edelen, Maria Orlando; Tucker, Joan S.; Stucky, Brian D.; Hansen, Mark; Cai, Li

    2014-01-01

    Introduction: Nicotine dependence is a core construct important for understanding cigarette smoking and smoking cessation behavior. This article describes analyses conducted to develop and evaluate item banks for assessing nicotine dependence among daily and nondaily smokers. Methods: Using data from a sample of daily (N = 4,201) and nondaily (N =1,183) smokers, we conducted a series of item factor analyses, item response theory analyses, and differential item functioning analyses (according to gender, age, and race/ethnicity) to arrive at a unidimensional set of nicotine dependence items for daily and nondaily smokers. We also evaluated performance of short forms (SFs) and computer adaptive tests (CATs) to efficiently assess dependence. Results: A total of 32 items were included in the Nicotine Dependence item banks; 22 items are common across daily and nondaily smokers, 5 are unique to daily smokers, and 5 are unique to nondaily smokers. For both daily and nondaily smokers, the Nicotine Dependence item banks are strongly unidimensional, highly reliable (reliability = 0.97 and 0.97, respectively), and perform similarly across gender, age, and race/ethnicity groups. SFs common to daily and nondaily smokers consist of 8 and 4 items (reliability = 0.91 and 0.81, respectively). Results from simulated CATs showed that dependence can be assessed with very good precision for most respondents using fewer than 6 items adaptively selected from the item banks. Conclusions: Nicotine dependence on cigarettes can be assessed on the basis of these item banks via one of the SFs, by using CATs, or through a tailored set of items selected for a specific research purpose. PMID:25118226

  19. Targeting nicotine addiction: the possibility of a therapeutic vaccine

    PubMed Central

    Escobar-Chávez, José Juan; Domínguez-Delgado, Clara Luisa; Rodríguez-Cruz, Isabel Marlen

    2011-01-01

    Cigarette smoking is the primary cause of lung cancer, cardiovascular diseases, reproductive disorders, and delayed wound healing all over the world. The goals of smoking cessation are both to reduce health risks and to improve quality of life. The development of novel and more effective medications for smoking cessation is crucial in the treatment of nicotine dependence. Currently, first-line smoking cessation therapies include nicotine replacement products and bupropion. The partial nicotinic receptor agonist, varenicline, has recently been approved by the US Food and Drug Administration (FDA) for smoking cessation. Clonidine and nortriptyline have demonstrated some efficacy, but side effects may limit their use to second-line treatment products. Other therapeutic drugs that are under development include rimonabant, mecamylamine, monoamine oxidase inhibitors, and dopamine D3 receptor antagonists. Nicotine vaccines are among newer products seeking approval from the FDA. Antidrug vaccines are irreversible, provide protection over years and need booster injections far beyond the critical phase of acute withdrawal symptoms. Interacting with the drug in the blood rather than with a receptor in the brain, the vaccines are free of side effects due to central interaction. For drugs like nicotine, which interacts with different types of receptors in many organs, this is a further advantage. Three anti-nicotine vaccines are today in an advanced stage of clinical evaluation. Results show that the efficiency of the vaccines is directly related to the antibody levels, a fact which will help to optimize the vaccine effect. The vaccines are expected to appear on the market between 2011 and 2012. PMID:21607018

  20. Molecular adsorption study of nicotine and caffeine on single-walled carbon nanotubes from first principles

    NASA Astrophysics Data System (ADS)

    Lee, Hyung-June; Kim, Gunn; Kwon, Young-Kyun

    2013-08-01

    Using first-principles calculations, we investigate the electronic structures and binding properties of nicotine and caffeine adsorbed on single-walled carbon nanotubes to determine whether CNTs are appropriate for filtering or sensing nicotine and caffeine molecules. We find that caffeine adsorbs more strongly than nicotine. The different binding characteristics are discussed by analyzing the modification of the electronic structure of the molecule-adsorbed CNTs. We also calculate the quantum conductance of the CNTs in the presence of nicotine or caffeine adsorbates and demonstrate that the influence of caffeine is stronger than nicotine on the conductance of the host CNT.

  1. Sensitivity of BN nano-cages to caffeine and nicotine molecules

    NASA Astrophysics Data System (ADS)

    Soltani, Alireza; Baei, Mohammad T.; Tazikeh Lemeski, E.; Shahini, Malihe

    2014-12-01

    Adsorption of caffeine and nicotine molecules over B12N12 and B16N16 nano-cages were investigated by using first-principles calculations to define whether BN nano-cages are applicable for filtering or sensing caffeine and nicotine molecules. The chemisorption energy of nicotine molecule on BN nano-cages is very stronger than caffeine molecule. Upon the adsorption of caffeine and nicotine molecules, the electronic properties of the BN nano-cages can be significantly changed, being too much sensitized on the caffeine and nicotine adsorptions.

  2. Evidence of Nicotine-Induced, Curare-Insensitive, Behavior in Planarians.

    PubMed

    Pagán, Oné R; Montgomery, Erica; Deats, Sean; Bach, Daniel; Baker, Debra

    2015-10-01

    Planarians are rapidly developing into very useful research subjects in pharmacology and neuroscience research. Here we report that curare, a cholinergic nicotinic receptor antagonist, alleviates the nicotine-induced planarian seizure-like movements (pSLM) by up to 50 % at equimolar concentrations of nicotine and curare (1 mM), while curare alone does not induce significant pSLMs. The simplest interpretation of our data is that there are nicotine induced behaviors insensitive to curare in our experimental organism. To the best of our knowledge, this is the first report on curare-insensitive, nicotine-induced effects in any organism. PMID:25614180

  3. Comparison of (/sup 3/H)nicotine and (/sup 3/H)acetylcholine binding in mouse brain: regional distribution

    SciTech Connect

    Sershen, H.; Reith, M.E.; Hashim, A.; Lajtha, A.

    1985-06-01

    In a continuing study of nicotine binding sites, the authors determined the relative amount of nicotine binding and acetylcholine binding in various brain regions of C57/BL and of DBA mice. Although midbrain showed the highest and cerebellum the lowest binding for both (/sup 3/H)nicotine and (/sup 3/H)acetylcholine, the ratio of nicotine to acetylcholine binding showed a three-fold regional variation. Acetylcholine inhibition of (/sup 3/H)nicotine binding indicated that a portion of nicotine binding was not inhibited by acetylcholine. These results indicate important differences between the binding of (+/-)-(/sup 3/H)nicotine and that of (/sup 3/H)acetylcholine.

  4. The nicotine paradox: effect of smoking on autonomic discrimination.

    PubMed

    Lombardo, T W; Epstein, L H

    1986-01-01

    Smoking reduces negative affect while it increases sympathetic nervous system activity. However, theories of emotion predict that increased autonomic arousal should increase rather than reduce negative affect. One explanation for this paradox is that nicotine interferes with perception of autonomic activity. We evaluated the effect of smoking on autonomic activity perception by measuring performance on a heartbeat detection task after a high or low dose of nicotine or not smoking. A group of nonsmokers also completed the task. Results failed to support the hypothesis. In light of previous research, the results suggest EMG perception may be more important to the negative affect reduction phenomenon than perception of autonomic activity. PMID:3739820

  5. Intelligent biomembranes for nicotine releases by radiation curing

    NASA Astrophysics Data System (ADS)

    Nakayama, Hiroshi; Kaetsu, Isao; Uchida, Kumao; Oishibashi, Manabu; Matsubara, Yoshio

    2003-06-01

    The authors have studied stimuli-responsive polyelectrolyte and polyampholyte hydrogels. Thermo-responsive copolymer hydrogels have also been studied. Recently, the authors have applied those hydrogels to radiation curable intelligent coatings for the gating of drug release channel. One way of this application is the coating on a drug including membrane to initiate and stop the drug release by on-off switching of stimulations. Some results of application to practical intelligent biomembranes such as glucose-responsive nicotine release membrane and temperature-responsive nicotine release membrane were investigated and their functions as well as of some effective factors on the release profiles were proved.

  6. Polyethylene glycol-based homologated ligands for nicotinic acetylcholine receptors☆

    PubMed Central

    Scates, Bradley A.; Lashbrook, Bethany L.; Chastain, Benjamin C.; Tominaga, Kaoru; Elliott, Brandon T.; Theising, Nicholas J.; Baker, Thomas A.; Fitch, Richard W.

    2010-01-01

    A homologous series of polyethylene glycol (PEG) monomethyl ethers were conjugated with three ligand series for nicotinic acetylcholine receptors. Conjugates of acetylaminocholine, the cyclic analog 1-acetyl-4,4-dimethylpiperazinium, and pyridyl ether A-84543 were prepared. Each series was found to retain significant affinity at nicotinic receptors in rat cerebral cortex with tethers of up to six PEG units. Such compounds are hydrophilic ligands which may serve as models for fluorescent/affinity probes and multivalent ligands for nAChR. PMID:19006672

  7. Randomized Single-Blinded Non-inferiority Trial Of 7 mg/kg Pentamidine Isethionate Versus 4 mg/kg Pentamidine Isethionate for Cutaneous Leishmaniaisis in Suriname

    PubMed Central

    Hu, Ricardo V. P. F.; Straetemans, Masja; Kent, Alida D.; Sabajo, Leslie O. A.; de Vries, Henry J. C.; Lai A Fat, Rudy F. M.

    2015-01-01

    Background Standard treatment of cutaneous leishmaniasis (CL) in Suriname entails three injections of pentamidine isethionate (PI) 4 mg/kg per injection in 7 days (7 day regimen). Compliance to treatment is low and may contribute to increasing therapy failure. A 3 day regimen, including 2 injections of 7 mg/kg in 3 days may increase compliance. Methods In a randomized, single-blinded non-inferiority trial conducted in Suriname, 84 CL patients received the 7 day regimen and 79 CL patients received the 3 day regimen. Primary objective was the proportion of patients clinically cured at 6 weeks follow-up. Secondary objectives were clinical cure at 12 weeks follow-up; parasitological cure at 6 and 12 weeks; adverse and drug related toxicity events recorded one week after the end of treatment and health related quality of life. The non-inferiority margin was set at 15%, 1 sided test, α = 0.1. Results At 6 weeks follow-up 31 (39%) patients in the 3 day regimen and 41 (49%) patients in the 7 day regimen were clinically cured. Intention to treat (ITT) analyses showed that the difference in proportion clinically cured was -9.6% (90% Confidence Interval (CI): -22.3% to 3.2%). Per protocol (PP) analysis showed that the difference in proportion clinically cured was 0.2% (90% CI: -14.6% to 15.2%). ITT analysis showed that the difference in proportion parasitological cured at 6 weeks was -15.2% (90% CI:-28.0% to -2.5%). PP analyses showed similar results. Non-inferiority could not be concluded for all adverse and toxicological events. Conclusion We cannot conclude that the 3 day regimen is non-inferior to the 7 day regimen regarding proportion clinically and parasitological cured. Therefore there is no evidence to change the current standard practice of the 7 day regimen for the treatment of CL in Suriname. PMID:25793773

  8. New quinoline derivatives as nicotinic receptor modulators.

    PubMed

    Manetti, Dina; Bellucci, Cristina; Dei, Silvia; Teodori, Elisabetta; Varani, Katia; Spirova, Ekaterina; Kudryavtsev, Denis; Shelukhina, Irina; Tsetlin, Victor; Romanelli, Maria Novella

    2016-03-01

    As a continuation of previous work on quinoline derivatives, which showed some preference (2-3 times) for the α7 with respect to α4β2 acetylcholine nicotinic receptors (nAChRs), we synthesized a series of novel azabicyclic or diazabicyclic compounds carrying a quinoline or isoquinoline ring, with the aim of searching for more selective α7 nAChR compounds. Radioligand binding studies on α7* and α4β2* nAChRs (rat brain homogenate) revealed one compound (7) with a 2-fold higher affinity for the α4β2*-subtype, and four compounds (11, 13, 14 and 16) with at least 3-fold higher affinity for α7* nAChR. The most promising was 11, showing Ki∼100 nM and over 10-fold selectivity for α7* nAChR. Compounds 7, 11, 13 and 16 at 50 μM suppressed ion currents induced in the rat α4β2 nAChR and the chimeric nAChR composed of the ligand-binding domain of the chick α7 and transmembrane domain of the α1 glycine receptor, expressed in Xenopus oocytes. Calcium imaging experiments on the human α7 nAChR expressed in the Neuro2a cells and potentiated by PNU-120596 confirmed the antagonistic activity for 7; on the contrary, 11, 13 and 16 were agonists with the EC50 values in the range of 1.0-1.6 μM. Thus, the introduced modifications allowed us to enhance the selectivity of quinolines towards α7 nAChR and to get novel compounds with agonistic activity. PMID:26840365

  9. Genetic and Pharmacokinetic Determinants of Response to Transdermal Nicotine in White, Black and Asian Non-Smokers

    PubMed Central

    Dempsey, Delia A.; St Helen, Gideon; Jacob, Peyton; Tyndale, Rachel F.; Benowitz, Neal L.

    2013-01-01

    The aim of the study was to examine genetic, pharmacokinetic and demographic factors that influence sensitivity to nicotine in never smokers. Sixty never smokers, balanced for gender and race (Caucasian, Blacks and Asian), wore 7 mg nicotine skin patches for up to 8 hours. Serial plasma nicotine concentrations and subjective and cardiovascular effects were measured, and genetic variation in the CYP2A6 gene, the primary enzyme responsible for nicotine metabolism, was assessed. Nicotine toxicity requiring patch removal developed in 9 subjects and was strongly associated with rate of rise and peak concentrations of plasma nicotine. Toxicity, subjective and cardiovascular effects of nicotine were associated with the presence of reduced function CYP2A6 alleles, presumably reflecting slow nicotine metabolic inactivation. This study has implications for understanding individual differences in responses to nicotine medications, particularly when the latter are used for treating medical conditions in non-smokers, and possibly in vulnerability to developing nicotine dependence. PMID:23933970

  10. Uncoupling nicotine mediated motoneuron axonal pathfinding errors and muscle degeneration in zebrafish

    SciTech Connect

    Welsh, Lillian; Tanguay, Robert L.; Svoboda, Kurt R.

    2009-05-15

    Zebrafish embryos offer a unique opportunity to investigate the mechanisms by which nicotine exposure impacts early vertebrate development. Embryos exposed to nicotine become functionally paralyzed by 42 hpf suggesting that the neuromuscular system is compromised in exposed embryos. We previously demonstrated that secondary spinal motoneurons in nicotine-exposed embryos were delayed in development and that their axons made pathfinding errors (Svoboda, K.R., Vijayaraghaven, S., Tanguay, R.L., 2002. Nicotinic receptors mediate changes in spinal motoneuron development and axonal pathfinding in embryonic zebrafish exposed to nicotine. J. Neurosci. 22, 10731-10741). In that study, we did not consider the potential role that altered skeletal muscle development caused by nicotine exposure could play in contributing to the errors in spinal motoneuron axon pathfinding. In this study, we show that an alteration in skeletal muscle development occurs in tandem with alterations in spinal motoneuron development upon exposure to nicotine. The alteration in the muscle involves the binding of nicotine to the muscle-specific AChRs. The nicotine-induced alteration in muscle development does not occur in the zebrafish mutant (sofa potato, [sop]), which lacks muscle-specific AChRs. Even though muscle development is unaffected by nicotine exposure in sop mutants, motoneuron axonal pathfinding errors still occur in these mutants, indicating a direct effect of nicotine exposure on nervous system development.

  11. 18-Methoxycoronaridine acts in the medial habenula to attenuate behavioral and neurochemical sensitization to nicotine.

    PubMed

    Eggan, Branden L; McCallum, Sarah E

    2016-07-01

    Systemic 18-methoxycoronaridine, an alpha3beta4 nicotinic antagonist, slows the rate of induction of behavioral sensitization to nicotine (Glick et al., 1996; 2011). The primary mechanism of action of 18-MC is believed to be the inhibition of α3β4 nicotinic acetylcholine receptors which are densely expressed in the medial habenula and interpeduncular nucleus (Pace et al., 2004; Glick et al., 2012). Recently, these habenular nicotinic receptors and their multiple roles in nicotine aversion and withdrawal have been increasingly emphasized (Antolin-Fontes et al., 2015). Here, we investigated the effects of 18-MC on both behavioral and neurochemical sensitization to nicotine. Daily systemic administration of 18-MC slowed the rate of induction of behavioral sensitization to nicotine but failed to block the expression of a sensitized locomotor response when absent. In contrast, in nicotine sensitized animals, systemic 18-MC significantly reduced the expression of behavioral sensitization. Results from intra-habenular administration of 18-MC paralleled these findings in that the expression of behavioral sensitization was also reduced in sensitized animals. Consistent with its effects on behavioral sensitization, intra-MHb treatment with 18-MC completely abolished sensitized dopamine responses in the nucleus accumbens in nicotine sensitized animals. These results show that α3β4 nicotinic receptors in the MHb contribute to nicotine sensitization, a phenomenon associated with drug craving and relapse. PMID:27059333

  12. Nicotine Inhibits Clostridium difficile Toxin A-Induced Colitis but Not Ileitis in Rats

    PubMed Central

    Vigna, Steven R.

    2016-01-01

    Nicotine is protective in ulcerative colitis but not Crohn's disease of the small intestine, but little is known about the effects of nicotine on Clostridium difficile toxin A-induced enteritis. Isolated ileal or colonic segments in anesthetized rats were pretreated with nicotine bitartrate or other pharmacological agents before intraluminal injection of toxin A. After 3 hours, the treated segments were removed and inflammation was assessed. Nicotine biphasically inhibited toxin A colitis but not ileitis. Pretreatment with the nicotinic receptor antagonist, hexamethonium, blocked the effects of nicotine. Pretreating the colonic segments with hexamethonium before toxin A administration resulted in more inflammation than seen with toxin A alone, suggesting that a tonic nicotinic anti-inflammatory condition exists in the colon. Nicotine also inhibited toxin A-induced increased colonic concentrations of the TRPV1 (transient receptor potential vanilloid subtype 1) agonist, leukotriene B4 (LTB4), and release of the proinflammatory neuropeptide, substance P. Pretreatment with nicotine did not protect against direct TRPV1-mediated colitis caused by intraluminal capsaicin. Nicotinic cholinergic receptors tonically protect the colon against inflammation and nicotine inhibits toxin A colitis but not toxin A ileitis in rats in part by inhibition of toxin A-induced activation of TRPV1 by endogenous TRPV1 agonists such as LTB4. PMID:26881175

  13. Nicotine absorption from electronic cigarette use: comparison between first and new-generation devices

    PubMed Central

    Farsalinos, Konstantinos E.; Spyrou, Alketa; Tsimopoulou, Kalliroi; Stefopoulos, Christos; Romagna, Giorgio; Voudris, Vassilis

    2014-01-01

    A wide range of electronic cigarette (EC) devices, from small cigarette-like (first-generation) to new-generation high-capacity batteries with electronic circuits that provide high energy to a refillable atomizer, are available for smokers to substitute smoking. Nicotine delivery to the bloodstream is important in determining the addictiveness of ECs, but also their efficacy as smoking substitutes. In this study, plasma nicotine levels were measured in experienced users using a first- vs. new-generation EC device for 1 hour with an 18 mg/ml nicotine-containing liquid. Plasma nicotine levels were higher by 35–72% when using the new- compared to the first-generation device. Compared to smoking one tobacco cigarette, the EC devices and liquid used in this study delivered one-third to one-fourth the amount of nicotine after 5 minutes of use. New-generation EC devices were more efficient in nicotine delivery, but still delivered nicotine much slower compared to tobacco cigarettes. The use of 18 mg/ml nicotine-concentration liquid probably compromises ECs' effectiveness as smoking substitutes; this study supports the need for higher levels of nicotine-containing liquids (approximately 50 mg/ml) in order to deliver nicotine more effectively and approach the nicotine-delivery profile of tobacco cigarettes. PMID:24569565

  14. An autoradiographic analysis of cholinergic receptors in mouse brain after chronic nicotine treatment

    SciTech Connect

    Pauly, J.R.; Marks, M.J.; Gross, S.D.; Collins, A.C. )

    1991-09-01

    Quantitative autoradiographic procedures were used to examine the effects of chronic nicotine infusion on the number of central nervous system nicotinic cholinergic receptors. Female DBA mice were implanted with jugular cannulas and infused with saline or various doses of nicotine (0.25, 0.5, 1.0 or 2.0 mg/kg/hr) for 10 days. The animals were then sacrificed and the brains were removed and frozen in isopentane. Cryostat sections were collected and prepared for autoradiographic procedures as previously described. Nicotinic cholinergic receptors were labeled with L-(3H)nicotine or alpha-(125I)bungarotoxin; (3H)quinuclidinyl benzilate was used to measure muscarinic cholinergic receptor binding. Chronic nicotine infusion increased the number of sites labeled by (3H)nicotine in most brain areas. However, the extent of the increase in binding as well as the dose-response curves for the increase were widely different among brain regions. After the highest treatment dose, binding was increased in 67 of 86 regions measured. Septal and thalamic regions were most resistant to change. Nicotinic binding measured by alpha-(125I)bungarotoxin also increased after chronic treatment, but in a less robust fashion. At the highest treatment dose, only 26 of 80 regions were significantly changes. Muscarinic binding was not altered after chronic nicotine treatment. These data suggest that brain regions are not equivalent in the mechanisms that regulate alterations in nicotinic cholinergic receptor binding after chronic nicotine treatment.

  15. Neuroscience of nicotine for addiction medicine: novel targets for smoking cessation medications.

    PubMed

    D'Souza, Manoranjan S

    2016-01-01

    Morbidity and mortality associated with tobacco smoking constitutes a significant burden on healthcare budgets all over the world. Therefore, promoting smoking cessation is an important goal of health professionals and policy makers throughout the world. Nicotine is a major psychoactive component in tobacco that is largely responsible for the widespread addiction to tobacco. A majority of the currently available FDA-approved smoking cessation medications act via neuronal nicotinic receptors. These medications are effective in approximately half of all the smokers, who want to quit and relapse among abstinent smokers continues to be high. In addition to relapse among abstinent smokers, unpleasant effects associated with nicotine withdrawal are a major motivational factor in continued tobacco smoking. Over the last two decades, animal studies have helped in identifying several neural substrates that are involved in nicotine-dependent behaviors including those associated with nicotine withdrawal and relapse to tobacco smoking. In this review, first the role of specific brain regions/circuits that are involved in nicotine dependence will be discussed. Next, the review will describe the role of specific nicotinic receptor subunits in nicotine dependence. Finally, the review will discuss the role of classical neurotransmitters (dopamine, serotonin, noradrenaline, glutamate, and γ-aminobutyric acid) as well as endogenous opioid and endocannabinoid signaling in nicotine dependence. The nicotinic and nonnicotinic neural substrates involved in nicotine-dependent behaviors can serve as possible targets for future smoking cessation medications. PMID:26806777

  16. Pathways and Networks-Based Analysis of Candidate Genes Associated with Nicotine Addiction

    PubMed Central

    Liu, Meng; Fan, Rui; Liu, Xinhua; Cheng, Feng; Wang, Ju

    2015-01-01

    Nicotine is the addictive substance in tobacco and it has a broad impact on both the central and peripheral nervous systems. Over the past decades, an increasing number of genes potentially involved in nicotine addiction have been identified by different technical approaches. However, the molecular mechanisms underlying nicotine addiction remain largely unclear. Under such situation, a comprehensive analysis focusing on the overall functional characteristics of these genes, as well as how they interact with each other will provide us valuable information to understand nicotine addiction. In this study, we presented a systematic analysis on nicotine addiction-related genes to identify the major underlying biological themes. Functional analysis revealed that biological processes and biochemical pathways related to neurodevelopment, immune system and metabolism were significantly enriched in the nicotine addiction-related genes. By extracting the nicotine addiction-specific subnetwork, a number of novel genes associated with addiction were identified. Moreover, we constructed a schematic molecular network for nicotine addiction via integrating the pathways and network, providing an intuitional view to understand the development of nicotine addiction. Pathway and network analysis indicated that the biological processes related to nicotine addiction were complex. Results from our work may have important implications for understanding the molecular mechanism underlying nicotine addiction. PMID:25965070

  17. Neurobiological mechanisms involved in nicotine dependence and reward: participation of the endogenous opioid system

    PubMed Central

    Berrendero, Fernando; Robledo, Patricia; Trigo, José Manuel; Martín-García, Elena; Maldonado, Rafael

    2010-01-01

    Nicotine is the primary component of tobacco that maintains the smoking habit and develops addiction. The adaptive changes of nicotinic acetylcholine receptors produced by repeated exposure to nicotine play a crucial role in the establishment of dependence. However, other neurochemical systems also participate in the addictive effects of nicotine including glutamate, cannabinoids, GABA and opioids. This review will cover the involvement of these neurotransmitters in nicotine addictive properties, with a special emphasis on the endogenous opioid system. Thus, endogenous enkephalins and beta-endorphins acting on mu-opioid receptors are involved in nicotine rewarding effects, whereas opioid peptides derived from prodynorphin participate in nicotine aversive responses. An upregulation of mu-opioid receptors has been reported after chronic nicotine treatment that could counteract the development of nicotine tolerance, whereas the downregulation induced on kappa-opioid receptors seems to facilitate nicotine tolerance. Endogenous enkephalins acting on mu-opioid receptors also play a role in the development of physical dependence to nicotine. In agreement with these actions of the endogenous opioid system, the opioid antagonist naltrexone has shown to be effective for smoking cessation in certain subpopulations of smokers. PMID:20170672

  18. Nicotine Intake From Electronic Cigarettes on Initial Use and After 4 Weeks of Regular Use

    PubMed Central

    Hajek, Peter; Phillips, Anna; Myers Smith, Katie; West, Oliver; McRobbie, Hayden

    2015-01-01

    Introduction: Electronic cigarettes (EC) have the potential to generate a substantial public health benefit if there is a switch from smoking to EC use on a population scale. The nicotine delivery from EC is likely to play a major role in their attractiveness to smokers. We assessed nicotine delivery from a first-generation EC and the effect of experience with its use on nicotine intake. Methods: Six smokers provided pharmacokinetic (PK) data after their first use of EC and again following 4 weeks of use. Results: The peak nicotine levels were achieved within 5min of starting the EC use, which suggests that EC may provide nicotine via pulmonary absorption. There were large individual differences in nicotine intake. Compared with the PK profile when using EC for the first time, 4 weeks of practice generated a 24% increase in the peak plasma concentrations (from 4.6 to 5.7ng/ml; nonsignificant) and a 79% increase in overall nicotine intake (AUC0→inf increased from 115 to 206 ng*min/ml; p < .05). Conclusions: First-generation EC provide faster nicotine absorption than nicotine replacement products, but to compete successfully with conventional cigarettes, EC may need to provide higher doses of nicotine. Nicotine intake from EC can increase with practice, but further studies are needed to confirm this effect. PMID:25122503

  19. Prior nicotine self-administration attenuates subsequent dopaminergic deficits of methamphetamine in rats: role of nicotinic acetylcholine receptors.

    PubMed

    Baladi, Michelle G; Nielsen, Shannon M; McIntosh, J Michael; Hanson, Glen R; Fleckenstein, Annette E

    2016-08-01

    Preclinical studies have demonstrated that oral nicotine exposure attenuates long-term dopaminergic damage induced by toxins, including repeated, high doses of methamphetamine. It is suggested that alterations in nicotinic acetylcholine receptor (nAChR) expression, including α4β2* and α6β2* subtypes, likely contribute to this protection. The current study extended these findings by investigating whether nicotine self-administration in male, Sprague-Dawley rats (a) attenuates short-term dopaminergic damage induced by methamphetamine and (b) causes alterations in levels of α4β2* and α6β2* nAChR subtypes. The findings indicate that nicotine self-administration (0.032 mg/kg/infusion for 14 days) per se did not alter α4β2* and α6β2* nAChR expression or dopamine transporter (DAT) expression and function. Interestingly, prior nicotine self-administration attenuated methamphetamine-induced decreases in DAT function when assessed 24 h, but not 1 h, after methamphetamine treatment (4×7.5 mg/kg/injection). The ability of nicotine to attenuate the effects of methamphetamine on DAT function corresponded with increases in α4β2*, but not α6β2*, nAChR binding density. Understanding the role of nAChRs in methamphetamine-induced damage has the potential to elucidate mechanisms underlying the etiology of disorders involving dopaminergic dysfunction, as well as to highlight potential new therapeutic strategies for prevention or reduction of dopaminergic neurodegeneration. PMID:26871405

  20. Effect of combined nicotine and shrapnel exposure on pain measures and gait after nerve injury.

    PubMed

    Rittenhouse, Bradley; Hill-Pryor, Crystal D; McConathy, Adam; Parker, Peter; Franco, Nelson; Toussaint, Esra; Barker, Darrell; Prasad, Balakrishna; Pizarro, Jose M

    2011-11-01

    A significant fraction of military soldiers sustain nerve injury and use tobacco or nicotine containing products. Healing of nerve injuries is influenced by many factors, such as degree of original injury, healing potential of the nerve, and general health of patient. However, recently, it has been demonstrated that the presence of retained insoluble metal fragments decreases healing. The effects of systemic nicotine administration, with or without metal fragments at the site of nerve injury, were evaluated. Both the nicotine-administered groups (nicotine, nicotine + shrapnel) showed significant increase in the peroneal function compared with untreated controls, as assessed by paw area (p < 0.05). Furthermore, to test possible role of altered sensory function, we used the hot plate assay. Latency to withdraw paw from a hot plate was significantly shorter in nicotine groups (p < 0.05). These data indicate that nicotine improves sensory and motor aspects of nerve function, in the presence or absence of shrapnel. PMID:22165666

  1. Using Basic Principles To Understand Complex Science: Nicotine Smoke Chemistry and Literature Analogies

    NASA Astrophysics Data System (ADS)

    Seeman, Jeffrey I.

    2005-10-01

    The Henderson Hasselbalch equation calculates the equilibrium distribution of 50:50 for nicotine in its nonprotonated (free base form), relative to its monoprotonated form, at pH of 8 in dilute aqueous solution. This ratio has then been used in the literature to predict the effect of ammonia compounds in tobacco and in smoke on nicotine pyrolysis and smoke chemistry. Experiments demonstrate that neither the thermal chemistry of tobacco alkaloids nor the transfer of nicotine from tobacco to smoke can be explained by the position of the nonprotonated versus monoprotonated form equilibrium in aqueous extracts of tobacco. The high thermal stability of nicotine in air allows nicotine salts to be converted to nonprotonated nicotine and volatilize during heating prior to any substantial decomposition of the nicotine moiety. In contrast, cocaine hydrochloride is thermally unstable and will rapidly decompose upon heating; cocaine hydrochloride must first be converted to its nonprotonated form prior to heating and volatilization.

  2. Ethanol-nicotine interactions in long-sleep and short-sleep mice

    SciTech Connect

    de Fiebre, C.M.; Marks, M.J.; Collins, A.C. )

    1990-05-01

    The possibility that common genetic factors regulate initial sensitivities to ethanol and nicotine as well as the development of cross-tolerance between these agents was explored using the long-sleep (LS) and short-sleep (SS) mice. The LS mice proved to be more sensitive to an acute challenge with nicotine than were the SS mice. Segregation analysis (F1, F2, backcross) indicated that ethanol sensitivity and nicotine sensitivity segregate together. Acute pretreatment with nicotine did not significantly affect sensitivity to ethanol, but ethanol pretreatment altered nicotine responsiveness. The LS mice develop more tolerance to nicotine and ethanol than do the SS and they also develop more cross-tolerance. These genetically determined differences in initial sensitivities, and tolerance and cross-tolerance development are not readily explained by differences in brain nicotinic receptor numbers.

  3. Nicotine and angiogenesis: a new paradigm for tobacco-related diseases.

    PubMed

    Cooke, John P; Bitterman, Haim

    2004-01-01

    The pathophysiology of tobacco-related diseases is complex and multifactorial. Among the approximately 4,000 compounds in tobacco smoke are carcinogens such as nitrosamines, irritants such as a variety of phenolic compounds, volatiles such as carbon monoxide, and of course nicotine. Nicotine itself has quite complex actions, mediated in part by nicotinic cholinergic receptors that may have extraneuronal, as well as neuronal distribution. This review discusses the mechanisms by which nicotine contributes to tobacco-related disease, with a focus on the surprising new finding that nicotine is a potent angiogenic agent. Nicotine hijacks an endogenous nicotinic cholinergic pathway present in endothelial cells that is involved in physiological, as well as pathological angiogenesis. PMID:15000345

  4. The selective dopamine D3 receptor antagonist SB-277011A reduces nicotine-enhanced brain reward and nicotine-paired environmental cue functions.

    PubMed

    Pak, Arlene C; Ashby, Charles R; Heidbreder, Christian A; Pilla, Maria; Gilbert, Jeremy; Xi, Zheng-Xiong; Gardner, Eliot L

    2006-10-01

    Increasing evidence suggests that enhanced dopamine (DA) neurotransmission in the nucleus accumbens (NAc) may play a role in mediating the reward and reinforcement produced by addictive drugs and in the attentional processing of drug-associated environmental cues. The meso-accumbens DA system is selectively enriched with DA D3 receptors, a DA receptor subtype increasingly implicated in reward-related brain and behavioural processes. From a variety of evidence, it has been suggested that selective DA D3 receptor antagonism may be a useful pharmacotherapeutic approach for treating addiction. The present experiments tested the efficacy of SB-277011A, a selective DA D3 receptor antagonist, in rat models of nicotine-enhanced electrical brain-stimulation reward (BSR), nicotine-induced conditioned locomotor activity (LMA), and nicotine-induced conditioned place preference (CPP). Nicotine was given subcutaneously within the dose range of 0.25-0.6 mg/kg (nicotine-free base). SB-277011A, given intraperitoneally within the dose range of 1-12 mg/kg, dose-dependently reduced nicotine-enhanced BSR, nicotine-induced conditioned LMA, and nicotine-induced CPP. The results suggest that selective D3 receptor antagonism constitutes a new and promising pharmacotherapeutic approach to the treatment of nicotine dependence. PMID:16942635

  5. Varenicline, a Partial Agonist at Neuronal Nicotinic Receptors, Reduces Nicotine-Induced Increases in 20% Ethanol Operant Self-Administration in Sprague-Dawley Rats

    PubMed Central

    Bito-Onon, Jade J.; Simms, Jeffrey A.; Chatterjee, Susmita; Holgate, Joan; Bartlett, Selena E.

    2010-01-01

    Alcohol and nicotine use disorders are often treated as separate diseases, despite evidence that approximately 80–90% of alcohol dependent individuals are also heavy smokers. Both nicotine and ethanol have been shown to interact with neuronal nicotinic acetylcholine receptors (nAChRs), suggesting these receptors are a common biological target for the effects of nicotine and ethanol in the brain. There are few studies that have examined the effects of co-administered nicotine and ethanol on the activity of nAChRs in rodents. In the present study, we show that Sprague-Dawley rats, a strain often used for nicotine studies but not as often for voluntary ethanol intake studies, will consume 20% ethanol using both the intermittent-access two-bottle-choice and operant self-administration models without the need for sucrose fading. We show that nicotine (0.2mg/kg and 0.8mg/kg, s.c.) significantly increases operant 20% ethanol self-administration and varenicline (2mg/kg, s.c), a partial agonist at nAChRs, significantly decreases operant ethanol self-administration and nicotine-induced increases in ethanol self-administration. This suggests that nAChRs play an important role in increasing ethanol self-administration and that varenicline may be an efficacious treatment for alcohol and nicotine co-dependencies. PMID:21392178

  6. Molybdenum-Containing Nicotine Hydroxylase Genes in a Nicotine Degradation Pathway That Is a Variant of the Pyridine and Pyrrolidine Pathways

    PubMed Central

    Yu, Hao; Li, Yangyang

    2015-01-01

    Ochrobactrum sp. strain SJY1 utilizes nicotine as a sole source of carbon, nitrogen, and energy via a variant of the pyridine and pyrrolidine pathways (the VPP pathway). Several strains and genes involved in the VPP pathway have recently been reported; however, the first catalyzing step for enzymatic turnover of nicotine is still unclear. In this study, a nicotine hydroxylase for the initial hydroxylation step of nicotine degradation was identified and characterized. The nicotine hydroxylase (VppA), which converts nicotine to 6-hydroxynicotine in the strain SJY1, is encoded by two open reading frames (vppAS and vppAL [subunits S and L, respectively]). The vppA genes were heterologously expressed in the non-nicotine-degrading strains Escherichia coli DH5α and Pseudomonas putida KT2440; only the Pseudomonas strain acquired the ability to degrade nicotine. The small subunit of VppA contained a [2Fe-2S] cluster-binding domain, and the large subunit of VppA contained a molybdenum cofactor-binding domain; however, an FAD-binding domain was not found in VppA. Resting cells cultivated in a molybdenum-deficient medium had low nicotine transformation activity, and excess molybdenum was detected in the purified VppA by inductively coupled plasma-mass spectrometry analysis. Thus, it is demonstrated that VppA is a two-component molybdenum-containing hydroxylase. PMID:26407884

  7. Cloning of Azorhizobium caulinodans nicotinate catabolism genes and characterization of their importance in N2 fixation.

    PubMed Central

    Buckmiller, L M; Lapointe, J P; Ludwig, R A

    1991-01-01

    Twenty Azorhizobium caulinodans vector insertion (Vi) mutants unable to catabolize nicotinate (Nic- phenotype) were identified and directly cloned as pVi plasmids. These pVi plasmids were used as DNA hybridization probes to isolate homologous wild-type sequences. From subsequent physical mapping experiments, the nic::Vi mutants defined four distinct loci. Two, possibly three, of these loci are physically linked. A. caulinodans nic loci II and III encode the structural genes for nicotinate catabolism; nic loci I and IV encode nicotinate-driven respiratory chain components. Recombinant lambda bacteriophages corresponding to three of these loci were subcloned in pRK293; resulting plasmids were used for complementation tests with resolved nic::IS50 derivatives of the nic::Vi mutants. When wild-type A. caulinodans was cultured in defined liquid medium under 3% O2, nicotinate catabolism stimulated N2 fixation 10-fold. In these exponentially growing cultures, the entire (300 microM) nicotinate supplement was exhausted within 10 h. While nic::Vi mutants retained the ability to fix some N2, they did so at rates only 10% of that of the wild type: nitrogenase activity by nic::Vi mutants was not stimulated by 300 microM added nicotinate. Higher-level (5 mM) nicotinate supplementation inhibited N2 fixation. Because 5 mM nicotinate repressed nitrogenase induction in all nic::Vi mutants as well, this repression was independent of nicotinate catabolism. During catabolism, nicotinate is first oxidized to 6-OH-nicotinate by a membrane-bound nicotinate hydroxylase which drives a respiratory chain to O2. In A. caulinodans wild-type cultures, added 300 microM 6-OH-nicotinate stimulated N2 fixation twofold better than did added 300 microM nicotinate. Likewise, nic::Vi mutant 61302, defective in nicotinate hydroxylase, fixed N2 at wild-type levels when supplemented with 300 microM 6-OH-nicotinate. Therefore, nicotinate catabolism stimulates N2 fixation not by nicotinate hydroxylase

  8. Smoking and Nicotine Replacement Treatment Issues Specific to Women.

    ERIC Educational Resources Information Center

    Pomerleau, Cynthia S.

    1996-01-01

    This paper examines gender differences in smoking that may lead to differential treatment process and outcome, suggesting ways to incorporate nicotine replacement products into treatment strategies adapted to the special needs of women smokers and discussing withdrawal symptomatology, maintaining abstinence, weight concerns, menstrual cycle…

  9. E-cigarettes for the management of nicotine addiction

    PubMed Central

    Knight-West, Oliver; Bullen, Christopher

    2016-01-01

    In this review, we discuss current evidence on electronic cigarettes (ECs), a rapidly evolving class of nicotine delivery system, and their role in managing nicotine addiction, specifically in helping smokers to quit smoking and/or reduce the amount of tobacco they smoke. The current evidence base is limited to three randomized trials (only one compares ECs with nicotine replacement therapy) and a growing number of EC user surveys (n=6), case reports (n=4), and cohort studies (n=8). Collectively, these studies suggest modest cessation efficacy and a few adverse effects, at least with the short-term use. On this basis, we provide advice for health care providers on providing balanced information for patients who enquire about ECs. More research, specifically well-conducted large efficacy trials comparing ECs with standard smoking cessation management (eg, nicotine replacement therapy plus behavioral support) and long-term prospective studies for adverse events, are urgently needed to fill critical knowledge gaps on these products. PMID:27574480

  10. Addressing Nicotine Dependence in Psychodynamic Psychotherapy: Perspectives from Residency Training

    ERIC Educational Resources Information Center

    Prochaska, Judith J.; Fromont, Sebastien C.; Banys, Peter; Eisendrath, Stuart J.; Horowitz, Mardi J.; Jacobs, Marc H.; Hall, Sharon M.

    2007-01-01

    Objective: According to APA treatment recommendations, psychiatrists should assess and intervene in tobacco use with all of their patients who smoke. The ease with which this occurs may vary by treatment model. This study examined perspectives in residency training to identify a framework for addressing nicotine dependence within psychodynamic…

  11. E-cigarettes for the management of nicotine addiction.

    PubMed

    Knight-West, Oliver; Bullen, Christopher

    2016-01-01

    In this review, we discuss current evidence on electronic cigarettes (ECs), a rapidly evolving class of nicotine delivery system, and their role in managing nicotine addiction, specifically in helping smokers to quit smoking and/or reduce the amount of tobacco they smoke. The current evidence base is limited to three randomized trials (only one compares ECs with nicotine replacement therapy) and a growing number of EC user surveys (n=6), case reports (n=4), and cohort studies (n=8). Collectively, these studies suggest modest cessation efficacy and a few adverse effects, at least with the short-term use. On this basis, we provide advice for health care providers on providing balanced information for patients who enquire about ECs. More research, specifically well-conducted large efficacy trials comparing ECs with standard smoking cessation management (eg, nicotine replacement therapy plus behavioral support) and long-term prospective studies for adverse events, are urgently needed to fill critical knowledge gaps on these products. PMID:27574480

  12. Nicotine Modulates the Long-Lasting Storage of Fear Memory

    ERIC Educational Resources Information Center

    Lima, Ramon H.; Radiske, Andressa; Kohler, Cristiano A.; Gonzalez, Maria Carolina; Bevilaqua, Lia R.; Rossato, Janine I.; Medina, Jorge H.; Cammarota, Martin

    2013-01-01

    Late post-training activation of the ventral tegmental area (VTA)-hippocampus dopaminergic loop controls the entry of information into long-term memory (LTM). Nicotinic acetylcholine receptors (nAChR) modulate VTA function, but their involvement in LTM storage is unknown. Using pharmacological and behavioral tools, we found that…

  13. Effect of transdermal nicotine administration on exercise endurance in men.

    PubMed

    Mündel, Toby; Jones, David A

    2006-07-01

    Nicotine is widely reported to increase alertness, improve co-ordination and enhance cognitive performance; however, to our knowledge there have been no attempts to replicate these findings in relation to exercise endurance. The purpose of this study was to determine the effects nicotine might have on cycling endurance, perception of exertion and a range of physiological variables. With local ethics committee approval and having obtained informed consent, 12 healthy, non-smoking men (22 +/- 3 years; maximal O2 uptake, 56 +/- 6 ml kg(-1) min(-1), mean +/- s.d.) cycled to exhaustion at 18 degrees C and 65% of their peak aerobic power, wearing either a 7 mg transdermal nicotine patch (NIC) or a colour-matched placebo (PLA) in a randomized cross-over design; water was available ad libitum. Subjects were exercising at approximately 75% of their maximal O2 uptake with no differences in cadence between trials. Ten out of 12 subjects cycled for longer with NIC administration, and this resulted in a significant 17 +/- 7% improvement in performance (P < 0.05). No differences were observed for perceived exertion, heart rate or ventilation. There were no differences in concentrations of plasma glucose, lactate or circulating fatty acids. In the absence of any effect on peripheral markers, we conclude that nicotine prolongs endurance by a central mechanism. Possible modes of action are suggested. PMID:16627574

  14. Neuronal nicotinic acetylcholine receptor modulation by general anesthetics.

    PubMed

    Flood, P; Role, L W

    1998-11-23

    1. General anesthetics have been shown to inhibit synaptic transmission in multiple areas of the central and peripheral nervous systems. 2. The mechanism of inhibition is not well understood. 3. It has become clear that general anesthetics modulate the function of members of the ligand gated ion channel superfamily, including receptors for GABA(A), glycine (Harrison et al., Mol. Pharmacol. 44(3), 1993, 628-632) and 5HT3 (Zhou and Lovinger, J. Pharmacol. Exp. Therap. 278(2), 1996, 732-740). 4. Studies of the activity of general anesthetics on recombinant neuronal nicotinic acetylcholine receptors have added this receptor family to those potently inhibited by general anesthetics (Flood et al., Anesthesiology 86(4), 1997, 859-865; Violet et al., Anesthesiology 86(4), 1997, 866-874). 5. Studies of neuronal nicotinic receptors in native neurons suggest that the inhibition of these receptors by general anesthetics at low clinical concentrations may be biologically significant (Nicoll, Science 199(4327), 1978, 451-452). 6. Recent work on neuronal nicotinic acetylcholine receptors in the central nervous system suggests that their primary role may be to modulate synaptic transmission (Role and Berg, Neuron 16(6), 1996, 1077-1085). 7. Thus, inhibition of nicotinic modulation in the central nervous system may result in inhibition of synaptic transmission and some of the behavioral consequences of general anesthesia. PMID:10049135

  15. Facts on Nicotine and Tobacco. Clearinghouse Fact Sheet.

    ERIC Educational Resources Information Center

    Slade, John

    Nicotine, the most abused drug in the United States, is the psychoactive drug in tobacco. It exerts diverse, often subtle effects on the central nervous system and can stimulate or relax, or do both simultaneously. Tolerance to this drug develops easily and addiction is common among people with other drug problems, especially alcoholism. Most…

  16. Passive exposure to nicotine from e-cigarettes.

    PubMed

    Gallart-Mateu, D; Elbal, L; Armenta, S; de la Guardia, M

    2016-05-15

    A procedure based on the use of ion mobility spectrometry (IMS), after liquid-liquid microextraction (LLME), has been successfully employed for the determination of passive exposure to nicotine from cigarette and e-cigarette smoking. Nicotine has been determined in exhaled breath and oral fluids of both, active and passive smokers. The aforementioned studies, made in closed environments, evidenced that the exhaled breath after conventional blend cigarette smoke provides nicotine levels of the order of 220ng per puff, in the case of experienced smokers, being exhaled only 32ng in the case of e-cigarettes. On the other hand, the nicotine amount in oral fluids of passive vapers was between 8 and 14µgL(-1) lower than the average value of 38±14µgL(-1) found for passive smokers of rolling tobacco and clearly lower than the 79±36µgL(-1) obtained from passive smokers of classical yellow blend. This study was also placed in the frame of the verification of the e-cigarettes composition. PMID:26992528

  17. Single molecule transistor based nanopore for the detection of nicotine

    SciTech Connect

    Ray, S. J.

    2014-12-28

    A nanopore based detection methodology was proposed and investigated for the detection of Nicotine. This technique uses a Single Molecular Transistor working as a nanopore operational in the Coulomb Blockade regime. When the Nicotine molecule is pulled through the nanopore area surrounded by the Source(S), Drain (D), and Gate electrodes, the charge stability diagram can detect the presence of the molecule and is unique for a specific molecular structure. Due to the weak coupling between the different electrodes which is set by the nanopore size, the molecular energy states stay almost unaffected by the electrostatic environment that can be realised from the charge stability diagram. Identification of different orientation and position of the Nicotine molecule within the nanopore area can be made from specific regions of overlap between different charge states on the stability diagram that could be used as an electronic fingerprint for detection. This method could be advantageous and useful to detect the presence of Nicotine in smoke which is usually performed using chemical chromatography techniques.

  18. Risk and Protective Factors for Nicotine Dependence in Adolescence

    ERIC Educational Resources Information Center

    Hu, Mei-Chen; Griesler, Pamela; Schaffran, Christine; Kandel, Denise

    2011-01-01

    Background: We investigated the role of psychosocial and proximal contextual factors on nicotine dependence in adolescence. Methods: Data on a multiethnic cohort of 6th to 10th graders from the Chicago public schools were obtained from four household interviews conducted with adolescents over two years and one interview with mothers. Structural…

  19. Physical Chemistry to the Rescue: Differentiating Nicotinic and Cholinergic Agonists

    ERIC Educational Resources Information Center

    King, Angela G.

    2005-01-01

    Researches suggest that two agonists can bind to the same binding site of an important transmembrane protein and elicit a biological response through strikingly different binding interactions. Evidence is provided which suggests two possible types of nicotinic acetylcholine receptor agonist binding like acetlycholine (cholinergic) or like nicotine…

  20. Single molecule transistor based nanopore for the detection of nicotine

    NASA Astrophysics Data System (ADS)

    Ray, S. J.

    2014-12-01

    A nanopore based detection methodology was proposed and investigated for the detection of Nicotine. This technique uses a Single Molecular Transistor working as a nanopore operational in the Coulomb Blockade regime. When the Nicotine molecule is pulled through the nanopore area surrounded by the Source(S), Drain (D), and Gate electrodes, the charge stability diagram can detect the presence of the molecule and is unique for a specific molecular structure. Due to the weak coupling between the different electrodes which is set by the nanopore size, the molecular energy states stay almost unaffected by the electrostatic environment that can be realised from the charge stability diagram. Identification of different orientation and position of the Nicotine molecule within the nanopore area can be made from specific regions of overlap between different charge states on the stability diagram that could be used as an electronic fingerprint for detection. This method could be advantageous and useful to detect the presence of Nicotine in smoke which is usually performed using chemical chromatography techniques.

  1. Modal gating of muscle nicotinic acetylcholine receptors

    NASA Astrophysics Data System (ADS)

    Vij, Ridhima

    Many ion channels exhibit multiple patterns of kinetic activity in single-channel currents. This behavior is rare in WT mouse muscle nicotinic acetylcholine receptors (AChRs), where A2C↔A2O gating events are well-described by single exponentials. Also, single-channel open probability (PO) is essentially homogeneous at a given agonist concentration in the WT receptors. Here I report that perturbations of almost all the residues in loop C (alpha188-alpha199, at the agonist binding site) generate heterogeneity in PO ('modes'). Such unsettled activity was apparent with an alanine substitution at all positions in loop C (except alphaY190 and alphaY198) and with different side chain substitutions at alphaP197 for both adult- and fetal-type AChRs. I used single channel electrophysiology along with site-directed mutagenesis to study modal gating in AChRs consequent to mutations/deletions in loop C. The multiple patterns of kinetic activity arose from the difference in agonist affinity rather than in intrinsic AChR gating. Out of the four different agonists used to study the modal behavior, acetylcholine (ACh) showed a higher degree of kinetic heterogeneity compared to others. The time constant for switching between modes was long (~mins), suggesting that they arise from alternative, stable protein conformations. By studying AChRs having only 1 functional binding site, I attempted to find the source of the affinity difference, which was traced mainly to the alphadelta agonist site. Affinity at the neurotransmitter binding site is mainly determined by a core of five aromatic residues (alphaY93, alphaW149, alphaY190, alphaY198 and deltaW57). Phenylalanine substitutions at all aromatic residues except alphaY93 resulted in elimination of modes. Modes were also eliminated by alanine mutation at deltaW57 on the complementary side but not at other aromatics. Also, by substituting four gamma subunit residues into the delta subunit on the complementary beta sheet, I found that

  2. RIC-3 differentially modulates α4β2 and α7 nicotinic receptor assembly, expression, and nicotine-induced receptor upregulation

    PubMed Central

    2013-01-01

    Background Recent work has shown that the chaperone resistant to inhibitors of acetylcholinesterase (RIC-3) is critical for the folding, maturation and functional expression of a variety of neuronal nicotinic acetylcholine receptors. α7 nicotinic receptors can only assemble and functionally express in select lines of cells, provided that RIC-3 is present. In contrast, α4β2 nicotinic receptors can functionally express in many cell lines even without the presence of RIC-3. Depending on the cell line, RIC-3 has differential effects on α4β2 receptor function – enhancement in mammalian cells but inhibition in Xenopus oocytes. Other differences between the two receptor types include nicotine-induced upregulation. When expressed in cell lines, α4β2 receptors readily and robustly upregulate with chronic nicotine exposure. However, α7 nicotinic receptors appear more resistant and require higher concentrations of nicotine to induce upregulation. Could the coexpression of RIC-3 modulate the extent of nicotine-induced upregulation not only for α7 receptors but also α4β2 receptors? We compared and contrasted the effects of RIC-3 on assembly, trafficking, protein expression and nicotine-induced upregulation on both α7 and α4β2 receptors using fluorescent protein tagged nicotinic receptors and Förster resonance energy transfer (FRET) microscopy imaging. Results RIC-3 increases assembly and cell surface trafficking of α7 receptors but does not alter α7 protein expression in transfected HEK293T cells. In contrast, RIC-3 does not affect assembly of α4β2 receptors but increases α4 and β2 subunit protein expression. Acute nicotine (30 min exposure) was sufficient to upregulate FRET between α4 and β2 subunits. Surprisingly, when RIC-3 was coexpressed with α4β2 receptors nicotine-induced upregulation was prevented. α7 receptors did not upregulate with acute nicotine in the presence or absence of RIC-3. Conclusions These results provide interesting novel data

  3. Localized low-level re-expression of high-affinity mesolimbic nicotinic acetylcholine receptors restores nicotine-induced locomotion but not place conditioning.

    PubMed

    Mineur, Y S; Brunzell, D H; Grady, S R; Lindstrom, J M; McIntosh, J M; Marks, M J; King, S L; Picciotto, M R

    2009-04-01

    High-affinity, beta2-subunit-containing (beta2*) nicotinic acetylcholine receptors (nAChRs) are essential for nicotine reinforcement; however, these nAChRs are found on both gamma-aminobutyric acid (GABA) and dopaminergic (DA) neurons in the ventral tegmental area (VTA) and also on terminals of glutamatergic and cholinergic neurons projecting from the pedunculopontine tegmental area and the laterodorsal tegmental nucleus. Thus, systemic nicotine administration stimulates many different neuronal subtypes in various brain nuclei. To identify neurons in which nAChRs must be expressed to mediate effects of systemic nicotine, we investigated responses in mice with low-level, localized expression of beta2* nAChRs in the midbrain/VTA. Nicotine-induced GABA and DA release were partially rescued in striatal synaptosomes from transgenic mice compared with tissue from beta2 knockout mice. Nicotine-induced locomotor activation, but not place preference, was rescued in mice with low-level VTA expression, suggesting that low-level expression of beta2* nAChRs in DA neurons is not sufficient to support nicotine reward. In contrast to control mice, transgenic mice with low-level beta2* nAChR expression in the VTA showed no increase in overall levels of cyclic AMP response element-binding protein (CREB) but did show an increase in CREB phosphorylation in response to exposure to a nicotine-paired chamber. Thus, CREB activation in the absence of regulation of total CREB levels during place preference testing was not sufficient to support nicotine place preference in beta2 trangenic mice. This suggests that partial activation of high-affinity nAChRs in VTA might block the rewarding effects of nicotine, providing a potential mechanism for the ability of nicotinic partial agonists to aid in smoking cessation. PMID:19077117

  4. Effects of environmental enrichment on ERK1/2 phosphorylation in the rat prefrontal cortex following nicotine-induced sensitization or nicotine self-administration

    PubMed Central

    Gomez, Adrian M.; Sun, Wei-Lun; Midde, Narasimha M.; Harrod, Steven B.; Zhu, Jun

    2014-01-01

    Rats raised in an enriched condition (EC) exhibit alterations in the neurobiological and behavioral response to nicotine compared to rats reared in an impoverished condition (IC) or a standard condition (SC). The current study determined whether environmental enrichment differentially regulates extracellular signal-regulated kinase1/2 (ERK1/2) activity in the prefrontal cortex (PFC) in rats following nicotine sensitization or nicotine self-administration. Under the saline control condition, EC rats displayed diminished baseline activity, and greater sensitization to repeated administration of nicotine compared to IC and SC rats. After repeated saline injections, the basal levels of phosphorylated ERK1/2 (pERK1/2) were higher in EC compared to IC and SC rats, which was negatively correlated with their respective baseline activities. Repeated nicotine (0.35 mg/kg) injections induced pERK1/2 to similar levels in SC and IC rats; however, the induction of pERK1/2 in EC rats by nicotine was not significantly different from saline controls, owing to their high baseline. In the self-administration paradigm, EC rats self-administered less nicotine (0.03 mg/kg/infusion) relative to IC or SC rats on a fixed ratio-1 schedule of reinforcement. Accordingly, no differences in pERK1/2 were found between EC and IC rats self-administering saline, whereas nicotine self-administration resulted in an increase in pERK1/2 in IC rats but not in EC rats. Furthermore, the levels of pERK1/2 in EC and IC rats were positively correlated with their respective total number of nicotine infusions. Thus, these findings suggest that environmental enrichment alters the basal and nicotine-mediated pERK1/2, which may contribute to enrichment-induced behavioral alterations in response to nicotine. PMID:25328101

  5. NICOTINE-RECEPTOR BLOCKADE AND THE EFFECTS OF ANATOXIN-A ON THE MOTOR ACTIVITY OF RATS: COMPARISON WITH NICOTINE.

    EPA Science Inventory

    Anatoxin-a is produced by several species of freshwater cyanobacteria and has caused several poisoning episodes in terrestrial and aquatic wildlife, livestock and domestic animals. Anatoxin-a is also a potent nicotinic agonist in the nervous system and at the neuromuscular juncti...

  6. Crocin Improves Damage Induced by Nicotine on A Number of Reproductive Parameters in Male Mice

    PubMed Central

    Salahshoor, Mohammad Reza; Khazaei, Mozafar; Jalili, Cyrus; Keivan, Mona

    2016-01-01

    Background Crocin, a carotenoid isolated from Crocus sativus L. (saffron), is a pharmacologically active component of saffron. Nicotine consumption can decrease fertility in males through induction of oxidative stress and DNA damage. The aim of this study is to determine the effects of crocin on reproductive parameter damages in male mice exposed to nicotine. Materials and Methods In this experimental study, we divided 48 mice into 8 groups (n=6 per group): control (normal saline), nicotine (2.5 mg/kg), crocin (12.5, 25 and 50 mg/kg) and crocin (12.5, 25 and 50 mg/kg)+nicotine (2.5 mg/kg). Mice received once daily intraperitoneal injections of crocin, nicotine and crocin+nicotine for 4 weeks. Sperm parameters (count, motility, and viability), testis weight, seminiferous tube diameters, testosterone, and serum nitric oxide levels were analyzed and compared. Results Nicotine administration significantly decreased testosterone level; sperm count, viability, and motility; testis weight and seminiferous tubule diameters compared to the control group (P<0.05). However, increasing the dose of crocin in the crocin and crocin+nicotine groups significantly boosted sperm motility and viability; seminiferous tubule diameters; testis weight; and testosterone levels in all groups compared to the nicotine group (P<0.05). Conclusion Crocin improves nicotine-induced adverse effects on reproductive parameters in male mice. PMID:27123203

  7. Antenatal Antioxidant Prevents Nicotine-Mediated Hypertensive Response in Rat Adult Offspring.

    PubMed

    Xiao, DaLiao; Huang, Xiaohui; Li, Yong; Dasgupta, Chiranjib; Wang, Lei; Zhang, Lubo

    2015-09-01

    Previous studies have demonstrated that perinatal nicotine exposure increased blood pressure (BP) in adult offspring. However, the underlying mechanisms were unclear. The present study tested the hypothesis that perinatal nicotine-induced programming of hypertensive response is mediated by enhanced reactive oxygen species (ROS) in the vasculature. Nicotine was administered to pregnant rats via subcutaneous osmotic mini-pumps from Day 4 of gestation to Day 10 after birth, in the absence or presence of the ROS inhibitor N-acetyl-cysteine (NAC) in the drinking water. Experiments were conducted in 8-mo-old male offspring. Perinatal nicotine treatment resulted in a significant increase in arterial ROS production in offspring, which was abrogated by NAC. Angiotensin II (Ang II)-induced BP responses were significantly higher in nicotine-treated group than in saline-treated control group, and NAC treatment blocked the nicotine-induced increase in BP response. Consistent with that, the nicotine treatment significantly increased both Ang II-induced and phorbol [12, 13]-dibutyrate (PDBu, a Prkc activator)-induced arterial contractions in adult offspring, which were blocked by NAC treatment. In addition, perinatal nicotine treatment significantly attenuated acetylcholine-induced arterial relaxation in offspring, which was also inhibited by NAC treatment. Results demonstrate that inhibition of ROS blocks the nicotine-induced increase in arterial reactivity and BP response to vasoconstrictors in adult offspring, suggesting a key role for increased oxidative stress in nicotine-induced developmental programming of hypertensive phenotype in male offspring. PMID:26224008

  8. The Predicted Impact of Reducing the Nicotine Content in Cigarettes on Alcohol Use

    PubMed Central

    Donny, Eric C.

    2014-01-01

    Introduction: Product standards reducing the level of nicotine in cigarettes could significantly improve public health by reducing smoking behavior and toxicant exposure. However, relatively little is known about how the regulatory strategy could impact alcohol use, a closely related health behavior that is also a major contributor to morbidity and mortality. The primary objective of this paper is to predict the effect of nicotine reduction on alcohol use, identify priorities for future research, and highlight areas for mitigating any adverse outcomes. Methods: We critically reviewed and integrated literatures examining the effects of very low nicotine content (VLNC) cigarettes on smoking-related outcomes (nicotine exposure, nicotine withdrawal, and smoking as a cue to drink) and, in turn, the effects of those outcomes on alcohol use. Results: Current evidence suggests reducing the nicotine content of cigarettes may benefit public health by reducing alcohol use and problematic drinking over time as a consequence of reduced exposure to nicotine and the smoking cues associated with drinking. Nicotine withdrawal could increase risk of drinking, although these effects should be short-lived and could be mitigated by other sources of nicotine. Gender, hazardous drinking, and psychiatric comorbidities are likely to be important moderators of the effects of VLNC cigarettes. Conclusions: It is imperative to broadly assess the public health impact of potential tobacco product regulations by including measures of closely related health behaviors that could be impacted by these interventions. Nicotine reduction in cigarettes may contribute to improved public health through reductions in alcohol use.

  9. Ameliorative effect of black tea on nicotine induced cardiovascular pathogenesis in rat

    PubMed Central

    Joukar, Siyavash; Shahouzehi, Beydolah; Najafipour, Hamid; Gholamhoseinian, Ahmad; Joukar, Farzin

    2012-01-01

    Regarding the role of nicotine in the development of cardiovascular complications of smoking, we investigated whether black tea has a modulatory effect on cardiovascular pathogenesis of nicotine in rat. Animals were randomized to control, tea, nicotine and tea plus nicotine groups. Test groups received black tea brewed (adding 400 ml boiling water to 10 g Lipton black tea for 5 min) orally alone or with nicotine 2 mg/kg/day, s.c. separately or combined for four weeks. On 28th day, lipids profile of blood and also malondialdehyde (MDA) level, glutathione peroxidase (GPx) activity and total antioxidant capacity (TAC) of heart tissue were measured. Nicotine administration caused a significant increase in total cholesterol, TG and HDL-C and also atherogenic index of plasma (log TG/HDL-C). Moreover, nicotine increased MDA level of heart. Black tea alone increased the antioxidant capacity of heart tissue without significant effect on lipid profile and MDA levels. Concomitant use of black tea and nicotine significantly attenuated the hyperlipidemic and atherogenic effects of nicotine but was unable to attenuate the MDA. Our findings suggest that black tea consumption reduces hyperlipidemia and atherogenesis as two cardiovascular risk factors and complications of nicotine, in rat. If these results can be extrapolated to human, smokers who daily drink black tea may be less at risk of cardiovascular disease.

  10. A CHRNA5 Smoking Risk Variant Decreases the Aversive Effects of Nicotine in Humans.

    PubMed

    Jensen, Kevin P; DeVito, Elise E; Herman, Aryeh I; Valentine, Gerald W; Gelernter, Joel; Sofuoglu, Mehmet

    2015-11-01

    Genome-wide association studies have implicated the CHRNA5-CHRNA3-CHRNB4 gene cluster in risk for heavy smoking and several smoking-related disorders. The heavy smoking risk allele might reduce the aversive effects of nicotine, but this hypothesis has not been tested in humans. We evaluated the effects of a candidate causal variant in CHRNA5, rs16969968, on the acute response to nicotine in European American (EA) and African American (AA) smokers (n=192; 50% AA; 73% male). Following overnight abstinence from nicotine, participants completed a protocol that included an intravenous (IV) dose of saline and two escalating IV doses of nicotine. The outcomes evaluated were the aversive, pleasurable, and stimulatory ratings of nicotine's effects, cardiovascular reactivity to nicotine, withdrawal severity, and cognitive performance before and after the nicotine administration session. The heavy smoking risk allele (rs16969968*A; frequency=28% (EA) and 6% (AA)) was associated with lower ratings of aversive effects (P<5 × 10(-8)) with marked specificity. This effect was evident in EA and AA subjects analyzed as separate groups and was most robust at the highest nicotine dose. Rs16969968*A was also associated with greater improvement on a measure of cognitive control (Stroop Task) following nicotine administration. These findings support differential aversive response to nicotine as one likely mechanism for the association of CHRNA5-CHRNA3-CHRNB4 with heavy smoking. PMID:25948103

  11. Effects of combined nicotine and fluoxetine treatment on adult hippocampal neurogenesis and conditioned place preference.

    PubMed

    Faillace, M P; Zwiller, J; Bernabeu, R O

    2015-08-01

    Adult neurogenesis occurs in mammals within the dentate gyrus, a hippocampal subarea. It is known to be induced by antidepressant treatment and reduced in response to nicotine administration. We checked here whether the antidepressant fluoxetine would inverse the decrease in hippocampal neurogenesis caused by nicotine. It is shown that repeated, but not a single injection of rats with fluoxetine was able to abolish the decrease in adult dentate cell proliferation produced by nicotine treatment. We measured the expression of several biochemical parameters known to be associated with neurogenesis in the dentate gyrus. Both drugs increased the expression of p75 neurotrophin receptor, which promotes proliferation and early maturation of dentate gyrus cells. Using the conditioned place preference (CPP) paradigm, we also gave both drugs in a context in which their rewarding properties could be measured. Fluoxetine produced a significant but less robust CPP than nicotine. A single injection of fluoxetine was found to reduce nicotine-induced CPP. Moreover, the rewarding properties of nicotine were completely abolished in response to repeated fluoxetine injections. Expression of nicotine-induced CPP was accompanied by an increase of phospho-CREB (cyclic AMP-responsive element-binding protein) and HDAC2 (histone deacetylase 2) expression in the nucleus accumbens. The data suggest that fluoxetine reward, as opposed to nicotine reward, depends on dentate gyrus neurogenesis. Since fluoxetine was able to disrupt the association between nicotine and the environment, this antidepressant may be tested as a treatment for nicotine addiction using cue exposure therapy. PMID:25981209

  12. Ascorbic Acid Ameliorates Nicotine Exposure Induced Impaired Spatial Memory Performance in Rats

    PubMed Central

    Sirasanagandla, SR; Rooben, RK; Rajkumar; Narayanan, SN; Jetti, R

    2014-01-01

    Introduction: The long lasting behavioural and cognitive impairments in offspring prenatally exposed to nicotine have been confirmed in animal models. In the present study, we investigated the effect of ascorbic acid on prenatal nicotine exposure induced behavioural deficits in male offspring of rats. Methods: The pregnant Wistar dams were divided into four groups of six rats: control, vehicle control, nicotine and nicotine+ascorbic acid groups. The nicotine group received daily dose of subcutaneous injections of 0.96 mg/kg body weight (bw) nicotine free base throughout gestation. Pregnant dams in nicotine+ascorbic acid group were first given nicotine free base (0.96 mg/kg bw/day; subcutaneous route) followed by ascorbic acid (50 mg/kg bw/day, orally) daily throughout gestation. The cognitive function of male offspring of all the experimental groups was studied using Morris water maze test at postnatal day 40. Results: Prenatal nicotine exposure altered spatial learning and memory in male offspring. However, treatment with ascorbic acid ameliorated these changes in rats. Conclusion: Ascorbic acid supplementation was found to be effective in preventing the prenatal nicotine exposure induced cognitive deficits in rat offspring to some extent. PMID:25429474

  13. Neuronal nicotinic receptors as brain targets for pharmacotherapy of drug addiction.

    PubMed

    Rahman, Shafiqur; López-Hernández, Gretchen Y; Corrigall, William A; Papke, Roger L

    2008-11-01

    Nicotine addiction and other forms of drug addiction continue to be significant public health problems in the United States and the rest of the world. Accumulated evidence indicates that brain nicotinic acetylcholine receptors (nAChRs) are a heterogenous family of ion channels expressed in the various parts of the brain. A growing body of preclinical studies suggests that brain nAChRs are critical targets for the development of pharmacotherapies for nicotine and other drug addictions. In this review, we will discuss the nAChR subtypes, their function in response to endogenous brain transmitters, and how their functions are regulated in the presence of nicotine. Furthermore, we will discuss the role of nAChRs in mediating nicotine-induced addictive behavior in animal models. Additionally, we will provide an overview of the effects of nicotine and nicotinic compounds on the mesolimbic dopamine system, part of the reinforcement/reward circuitry of the brain, as an example of the neurochemical basis of nicotine addiction and other drug addictions. An appreciation of the complexity of nicotinic receptors and their regulation will be necessary for the development of nicotinic receptor modulators as potential pharmacotherapy for drug addiction. PMID:19128201

  14. Cadmium Increases the Sensitivity of Adolescent Female Mice to Nicotine-Related Behavioral Deficits

    PubMed Central

    Adeniyi, Philip Adeyemi; Olatunji, Babawale Peter; Ishola, Azeez Olakunle; Ajonijebu, Duyilemi Chris; Ogundele, Olalekan Michael

    2014-01-01

    This study investigates spatial and nonspatial working memory, anxiety related behavior, and motor activities in cadmium and/or nicotine exposed female adolescent mice. P28 female adolescent mice (albino strain) were divided into four groups of five (n = 5) mice each. A set of mice (Nic) received subcutaneous nicotine (2.0 mg/kg) while a separate set (Cd) was treated with 2.0 mg/kg cadmium (subcutaneous). For the combined treatments of cadmium and nicotine, we administered 2.0 mg/kg Nicotine and 2.0 mg/kg of Cd. Subsequently, a separate group of animals (n = 5; control) received normal saline. The total duration of treatment for all groups was 28 days (P28–P56). At P56, the treatment was discontinued, after which the animals were examined in behavioural tests. Nicotine and cadmium increased the metabolism and food intake in the female adolescent mice. This also corresponded to an increase in weight when compared with the control. However, a combined nicotine-cadmium treatment induced a decline in weight of the animals versus the control. Also, nicotine administration increased the motor function, while cadmium and nicotine-cadmium treatment caused a decline in motor activity. Both nicotine and cadmium induced a reduction in memory index; however, nicotine-cadmium treatment induced the most significant decrease in nonspatial working memory. PMID:25477708

  15. Nicotine reinforcement is reduced by cannabinoid CB1 receptor blockade in the ventral tegmental area.

    PubMed

    Simonnet, Amelie; Cador, Martine; Caille, Stephanie

    2013-11-01

    Cannabinoid type 1 (CB1) receptors control the motivational properties and reinforcing effects of nicotine. Indeed, peripheral administration of a CB1 receptor antagonist dramatically decreases both nicotine taking and seeking. However, the neural substrates through which the cannabinoid CB1 receptors regulate the voluntary intake of nicotine remain to be elucidated. In the present study, we sought to determine whether central injections of a CB1 receptor antagonist delivered either into the ventral tegmental area (VTA) or the nucleus accumbens (NAC) may alter nicotine intravenous self-administration (IVSA). Rats were first trained to self-administer nicotine (30 μg/kg/0.1 ml). The effect of central infusions of the CB1 antagonist AM 251 (0, 1 and 10 μg/0.5 μl/side) on nicotine-taking behavior was then tested. Intra-VTA infusions of AM 251 dose dependently reduced IVSA with a significant decrease for the dose 10 μg/0.5 μl/side. Moreover, operant responding for water was unaltered by intra-VTA AM 251 at the same dose. Surprisingly, intra-NAC delivery of AM 251 did not alter nicotine behavior at all. These data suggest that in rats chronically exposed to nicotine IVSA, the cannabinoid CB1 receptors located in the VTA rather than in the NAC specifically control nicotine reinforcement and, subsequently, nicotine-taking behavior. PMID:22784230

  16. The Reinforcement Threshold for Nicotine as a Target for Tobacco Control

    PubMed Central

    Sofuoglu, Mehmet; LeSage, Mark G.

    2012-01-01

    BACKGROUND Cigarette smoking represents an enormous public health problem worldwide that leads to over 5 million deaths per year. The gradual reduction of the nicotine content of cigarettes below the threshold that is required to develop addiction is one strategy that might substantially reduce the number of addicted smokers and prevent adolescents from becoming addicted to nicotine (Benowitz and Henningfield 1994). While the potential public health benefits of this approach are enormous, the guiding concepts and relevant empirical evidence needed to support the implementation of a nicotine reduction policy require a critical examination. METHODS The purpose of this paper is to briefly review the current concepts and research regarding nicotine reduction while also discussing the utility of the addictive threshold for nicotine in this approach. The accurate determination of the nicotine addiction threshold presents some conceptual challenges as there is a lack of consensus on how to best measure nicotine addiction. This difficulty can impede the progress for developing a science-based tobacco control policy. As an alternative, the nicotine reinforcement threshold is a relatively clear concept, and well-accepted methods and criteria are available to measure nicotine reinforcement. RESULTS However, there are many gaps in our current knowledge concerning the nicotine reinforcement threshold in humans. The threshold for nicotine reinforcement remains to be determined in controlled settings using different populations of current or potential tobacco users. In addition, the value of the nicotine reinforcement threshold in predicting tobacco use in real-world settings needs to be examined. The results of such studies will determine the potential utility of the estimated threshold for nicotine reinforcement in developing science-based tobacco control policies. PMID:22622242

  17. Adolescent alcohol exposure decreased sensitivity to nicotine in adult Wistar rats.

    PubMed

    Boutros, Nathalie; Semenova, Svetlana; Markou, Athina

    2016-07-01

    Many adolescents engage in heavy alcohol use. Limited research in humans indicates that adolescent alcohol use predicts adult tobacco use. The present study investigated whether adolescent intermittent ethanol (AIE) exposure alters nicotine sensitivity in adulthood. Adolescent male Wistar rats (postnatal day 28-53) were exposed to AIE exposure that consisted of 5 g/kg of 25 percent ethanol three times per day in a 2 days on/2 days off regimen. Control rats received water with the same exposure regimen. In adulthood, separate groups of rats were tested for nicotine intravenous self-administration (IVSA), drug discrimination and conditioned taste aversion (CTA). The dose-response function for nicotine IVSA under a fixed-ratio schedule of reinforcement was similar in AIE-exposed and control rats. However, AIE-exposed rats self-administered less nicotine at the lowest dose, suggesting that low-dose nicotine was less reinforcing in AIE-exposed, compared with control rats. AIE-exposed rats self-administered less nicotine under a progressive-ratio schedule, suggesting decreased motivation for nicotine after AIE exposure. The discriminative stimulus effects of nicotine were diminished in AIE-exposed rats compared with control rats. No group differences in nicotine CTA were observed, suggesting that AIE exposure had no effect on the aversive properties of nicotine. Altogether, these results demonstrate that AIE exposure decreases sensitivity to the reinforcing, motivational and discriminative properties of nicotine while leaving the aversive properties of nicotine unaltered in adult rats. These findings suggest that drinking during adolescence may result in decreased sensitivity to nicotine in adult humans, which may in turn contribute to the higher rates of tobacco smoking. PMID:25950618

  18. Blockade of cholinergic transmission elicits somatic signs in nicotine-naïve adolescent rats

    PubMed Central

    Schmidt, Clare E.; Manbeck, Katherine E.; Shelley, David; Harris, Andrew C.

    2015-01-01

    High doses of the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine can elicit somatic signs resembling those associated with nicotine withdrawal in nicotine-naïve adult rats. Understanding this phenomenon, and its possible modulation by acute nicotine and age, could inform the use of mecamylamine as both an experimental tool and potential pharmacotherapy for tobacco dependence and other disorders. This study evaluated the ability of high-dose mecamylamine to elicit somatic signs in adolescent rats, and the potential for acute nicotine pretreatment to potentiate this effect as previously reported in adults. Single or repeated injections of mecamylamine (1.5 or 3.0 mg/kg, s.c.) elicited somatic signs in nicotine-naïve adolescents, but this effect was not influenced by 2 h pretreatment with acute nicotine (0.5 mg/kg, s.c.). In an initial evaluation of the effects of age in this model, mecamylamine (2.25 mg/kg, s.c.) elicited somatic signs in nicotine-naïve adolescents and adults. This effect was modestly enhanced following acute nicotine injections in adults but not in adolescents, even when a higher nicotine dose (1.0 rather than 0.5 mg/kg, s.c.) was used in adolescents to account for age differences in nicotine pharmacokinetics. These studies are the first to show that mecamylamine elicits somatic signs in nicotine-naïve adolescent rats, an effect that should be considered when designing and interpreting studies examining effects of high doses of mecamylamine in adolescents. Our findings also provide preliminary evidence that these signs may be differentially modulated by acute nicotine pretreatment in adolescents versus adults. PMID:26539119

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

    PubMed

    Schweitzer, Kelly S; Chen, Steven X; Law, Sarah; Van Demark, Mary; Poirier, Christophe; Justice, Matthew J; Hubbard, Walter C; Kim, Elena S; Lai, Xianyin; Wang, Mu; Kranz, William D; Carroll, Clinton J; Ray, Bruce D; Bittman, Robert; Goodpaster, John; Petrache, Irina

    2015-07-15

    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. PMID:25979079

  20. Estrogen provokes the depressant effect of chronic nicotine on vagally mediated reflex chronotropism in female rats.

    PubMed

    El-Mas, Mahmoud M; El-Gowelli, Hanan M; El-Gowilly, Sahar M; Fouda, Mohamed A; Helmy, Mai M

    2012-08-01

    We recently reported that acute nicotine impairs reflex tachycardic activity in estrogen-depleted, but not estrogen-repleted, female rats, suggesting a restraining influence for estrogen against the nicotine effect. In this study, we tested whether the baroreflex-protective effect of estrogen can be replicated when nicotine was administered chronically. We also report on the dose dependence and autonomic modulation of the nicotine-baroreflex interaction. The effects of nicotine (0.5, 1, or 2 mg/kg/day for 14 days) on baroreflex curves relating changes in heart rate to increases [phenylephrine (PE)] or decreases [sodium nitroprusside (SNP)] in blood pressure were evaluated in sham-operated (SO), ovariectomized (OVX), and estrogen-replaced OVX (OVXE(2)) rats. Slopes of the curves were taken as a measure of baroreflex sensitivity (BRS(PE) and BRS(SNP)). In SO rats, both reflex bradycardic and tachycardic responses were attenuated by nicotine in a dose-related fashion. In nicotine-treated rats, blockade of β-adrenergic (propranolol), but not muscarinic (atropine), receptors caused additional reductions in reflex chronotropic responses, implying that nicotine selectively impairs reflex vagal activity. OVX selectively decreased BRS(PE) but not BRS(SNP) and abolished the nicotine-induced impairment of either response. These effects of OVX were reversed after treatment with estrogen or the estrogen receptor modulator raloxifene. In atropine-treated rats, comparable BRS values were demonstrated in all rat preparations regardless of the estrogen or nicotine milieu. Collectively, the inhibition of vagal activity accounts for the depressant effect of chronic nicotine on baroreflex activity. Furthermore, contrary to nicotine's acute effects, the baroreflex-attenuating effect of chronic nicotine is exacerbated by estrogen. PMID:22619254

  1. Occupational secondhand smoke is the main determinant of hair nicotine concentrations in bar and restaurant workers

    PubMed Central

    Iglesias, Verónica; Erazo, Marcia; Droppelmann, Andrea; Steenland, Kyle; Aceituno, Paulina; Orellana, Cecilia; Acuña, Marisol; Peruga, Armando; Breysse, Patrick N.; Navas-Acien, Ana

    2015-01-01

    Objective To evaluate the relative contribution of occupational vs. non-occupational secondhand tobacco smoke exposure to overall hair nicotine concentrations in non-smoking bar and restaurant employees. Method We recruited 76 non-smoking employees from venues that allowed smoking (n = 9), had mixed policies (smoking and non-smoking areas, n = 13) or were smoke-free (n = 2) between April and August 2008 in Santiago, Chile. Employees used personal air nicotine samplers during working and non-working hours for a 24-h period to assess occupational vs. non-occupational secondhand tobacco smoke exposure and hair nicotine concentrations to assess overall secondhand tobacco smoke exposure. Results Median hair nicotine concentrations were 1.5 ng/mg, interquartile range (IQR) 0.7 to 5.2 ng/mg. Time weighted average personal air nicotine concentrations were higher during working hours (median 9.7, IQR 3.3-25.4 μg/m3) compared to non-working hours (1.7, 1.0-3.1 μg/m3). Hair nicotine concentration was best predicted by personal air nicotine concentration at working hours. After adjustment, a 2-fold increase in personal air nicotine concentration in working hours was associated with a 42% increase in hair nicotine concentration (95% confidence interval 14-70%). Hair nicotine concentration was not associated with personal air nicotine concentration during non-working hours (non-occupational exposure). Conclusions Personal air nicotine concentration at working hours was the major determinant of hair nicotine concentrations in non-smoking employees from Santiago, Chile. Secondhand tobacco smoke exposure during working hours is a health hazard for hospitality employees working in venues where smoking is allowed. PMID:24813578

  2. Early adolescent nicotine exposure affects later-life cocaine reward in mice.

    PubMed

    Alajaji, Mai; Lazenka, Matthew F; Kota, Dena; Wise, Laura E; Younis, Rabha M; Carroll, F Ivy; Levine, Amir; Selley, Dana E; Sim-Selley, Laura J; Damaj, M Imad

    2016-06-01

    Adolescence represents a unique developmental period associated with increased risk-taking behavior and experimentation with drugs of abuse, in particular nicotine. We hypothesized that exposure to nicotine during early adolescence might increase the risk for drug reward in adulthood. To test this hypothesis, male ICR mice were treated with a subchronic regimen of nicotine or saline during adolescence, and their preference for cocaine, morphine and amphetamine was examined using the conditioned place preference (CPP) test in adulthood. Long-term behavioral changes induced by nicotine suggested a possible role of altered gene transcription. Thus, immunoblot for ΔFosB, a member of the Fos family of transcription factors, was conducted in the nucleus accumbens of these mice. Mice treated with nicotine during early but not late adolescence showed an increase in CPP for cocaine, morphine and amphetamine later in adulthood. This effect was not seen in mice pretreated with a subchronic regimen of nicotine as adults, suggesting that exposure to nicotine specifically during early adolescence increases the rewarding effects of other drugs in adulthood. However, adolescent nicotine exposure did not alter highly palatable food conditioning in mice. The enhancement of cocaine CPP by nicotine was strain-dependent and was blocked by pretreatment with nicotinic antagonists. In addition, nicotine exposure during early adolescence induced ΔFosB expression to a greater extent than identical nicotine exposure in adulthood, and enhanced cocaine-induced locomotor sensitization later in adulthood. These results suggest that nicotine exposure during early adolescence increases drug-induced reward in adulthood through mechanisms that may involve the induction of ΔFosB. PMID:26808314

  3. Motoneuron axon pathfinding errors in zebrafish: differential effects related to concentration and timing of nicotine exposure.

    PubMed

    Menelaou, Evdokia; Paul, Latoya T; Perera, Surangi N; Svoboda, Kurt R

    2015-04-01

    Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMNs). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15-30 μM). Previous work showed that the paralytic mutant zebrafish known as sofa potato exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. PMID:25668718

  4. Nicotine-Induced Modulation of the Cholinergic Twitch Response in the Ileum of Guinea Pig.

    PubMed

    Donnerer, Josef; Liebmann, Ingrid

    2015-01-01

    In the present study, the direct drug effects of nicotine and its effects on the cholinergic twitch responses of the electrically stimulated longitudinal muscle-myenteric plexus strip from the ileum of guinea pig were investigated. Nicotine dose-dependently (0.3-10 µmol/l) evoked the well-known contractile responses on its own. Whereas the interposed twitch responses remained present without a change in height at 1 µmol/l nicotine, a nicotine concentration of 3 µmol/l slightly and a concentration of 10 µmol/l markedly diminished the twitch during their presence. After the washout of 1-10 µmol/l nicotine, the height of the twitch response was also temporarily and significantly reduced by 30-77%. The P2X purinoceptor agonist αβ-methylene ATP (1-10 µmol/l) dose-dependently induced contractions on its own and reduced the twitch response during its presence in the organ bath; however, it did not diminish the twitch responses after washout of the drug as nicotine did. The P2X antagonist pyridoxalphosphate-6-azophenyl-2'-4'-disulphonic acid, the NMDA channel blocker MK-801 and the inhibitor of small conductance Ca(2+)-activated K(+) (SK) channels apamin reduced the contractile effect of 1 µmol/l nicotine. Apamin also significantly prevented the 'post-nicotine inhibition of the twitch' following the washout of 1-3 µmol/l nicotine. As a conclusion, we provide evidence for a functional interaction between nicotinic receptors and the P2X receptors in the ileum of the guinea pig. The 'post-nicotine inhibition of the twitch' is not due to nicotinic acetylcholine receptor desensitization or transmitter depletion, but most probably the secondary effects of nicotine on SK channels determine the reduced cholinergic motor neuron excitability. PMID:26088942

  5. Tobacco extract but not nicotine impairs the mechanical strength of fracture healing in rats.

    PubMed

    Skott, Martin; Andreassen, Troels T; Ulrich-Vinther, Michael; Chen, X; Keyler, Dan E; LeSage, Mark G; Pentel, Paul R; Bechtold, Joan E; Soballe, Kjeld

    2006-07-01

    The influence of nicotine and tobacco extract (without nicotine) alone and in combination on and mechanical strength of closed femoral fractures in rats was investigated. One hundred four male Sprague-Dawley rats were divided into four groups receiving: nicotine, tobacco extract, tobacco extract plus nicotine, and saline. One week prior to fracture, osmotic pumps were implanted subcutaneously in all animals to administer nicotine equivalent to the serum level of nicotine observed in a smoker consuming one to two packs of cigarettes daily. An equivalent volume of saline was administered to the control animals. Tobacco extract was administered orally. A closed transverse femoral diaphysial fracture was performed, and stabilized with an intramedullary pin. The fractures were mechanically tested after 21 days of healing. Tobacco extract alone decreased the mechanical strength. Ultimate torque and torque at yield point of the tobacco extract group were decreased by 21% (p=0.010) and 23% (p=0.056), respectively, compared with the vehicle (saline) group, and by 20% (p=0.023) and 26% (p=0.004), respectively, compared with the nicotine group. No difference was found between the tobacco extract and tobacco extract plus nicotine groups. An 18% (p=0.013) reduction in torque at yield point was observed in the tobacco extract plus nicotine group compared with the nicotine group. No differences in ultimate stiffness, energy absorption, and callus bone mineral content at the fracture line were found between any of the groups. Serum levels of nicotine were between 40-50 ng/mL in the group given nicotine alone and the group given tobacco extract plus nicotine (equivalent to serum levels observed in persons smoking one to two packs of cigarettes per day). PMID:16705735

  6. Enhanced nicotine self-administration and suppressed dopaminergic systems in a rat model of diabetes

    PubMed Central

    O'Dell, Laura E.; Natividad, Luis A.; Pipkin, Joseph A.; Roman, Francisco; Torres, Ivan; Jurado, Jesus; Torres, Oscar V.; Friedman, Theodore C.; Tenayuca, John M.; Nazarian, Arbi

    2013-01-01

    Patients with diabetes display a heightened propensity to use tobacco; however, it is unclear whether they experience enhanced rewarding effects of nicotine. Thus, this study examined the reinforcing effects of nicotine in a rodent model of diabetes involving administration of streptozotocin (STZ), a drug that is toxic to pancreatic insulin-producing cells. The first study compared STZ- and vehicle-treated rats that had 23-hour access to intravenous self-administration (IVSA) of nicotine or saline and concomitant access to food and water. In order to examine the contribution of dopamine to our behavioral effects, dopamine transporter (DAT), D1 and D2 receptor levels were compared in the nucleus accumbens (NAc) following 10 days of nicotine or saline IVSA. Dopamine levels in the NAc were also compared following nicotine administration. Lastly, nicotine metabolism and dose-dependent effects of nicotine IVSA were assessed. The results revealed that STZ-treated rats displayed enhanced nicotine intake and a robust increase in food and water intake relative to controls. Protein analysis revealed an increase in DAT and a decrease in D1 receptor levels in the NAc of STZ- versus vehicle-treated rats regardless of IVSA condition. STZ-treated rats also displayed suppressed NAc dopamine levels during baseline and in response to nicotine. STZ treatment did not alter our assessment of nicotine metabolism. Furthermore, STZ treatment increased nicotine IVSA in a dose-dependent manner. Our findings suggest that STZ-treatment increased the rewarding effects of nicotine. This suggests that strong reinforcing effects of nicotine may contribute to greater tobacco use in patients with diabetes. PMID:23834715

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

    PubMed Central

    Schweitzer, Kelly S.; Chen, Steven X.; Law, Sarah; Van Demark, Mary; Poirier, Christophe; Justice, Matthew J.; Hubbard, Walter C.; Kim, Elena S.; Lai, Xianyin; Wang, Mu; Kranz, William D.; Carroll, Clinton J.; Ray, Bruce D.; Bittman, Robert; Goodpaster, John

    2015-01-01

    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. PMID:25979079

  8. Nicotine primes the effect of cocaine on the induction of LTP in the amygdala.

    PubMed

    Huang, Yan-You; Kandel, Denise B; Kandel, Eric R; Levine, Amir

    2013-11-01

    In human populations, there is a well-defined sequence of involvement in drugs of abuse, in which the use of nicotine or alcohol precedes the use of marijuana, which in turn, precedes the use of cocaine. The term "Gateway Hypothesis" describes this developmental sequence of drug involvement. In prior work, we have developed a mouse model to study the underlying metaplastic behavioral, cellular and molecular mechanisms by which exposure to one drug, namely nicotine, affects the response to another drug, namely cocaine. We found that nicotine enhances significantly the changes in synaptic plasticity in the striatum induced by cocaine (Levine et al., 2011). Here we ask: does the metaplastic effect of nicotine on cocaine also apply in the amygdala, a brain region that is involved in the orchestration of emotions and in drug addiction? We find that pretreatment with nicotine enhances long-term synaptic potentiation (LTP) in response to cocaine in the amygdala. Both short-term (1 day) and long-term (7 days) pre-exposure to nicotine facilitate the induction of LTP by cocaine. The effect of nicotine on LTP is unidirectional; exposure to nicotine following treatment with cocaine is ineffective. This metaplastic effect of nicotine on cocaine is long lasting but reversible. The facilitation of LTP can be obtained for 24 but not 40 days after cessation of nicotine. As is the case in the striatum, pretreatment with Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, simulates the priming effect of nicotine. These results provide further evidence that the priming effect of nicotine may be achieved, at least partially, by the inhibition of histone acetylation and indicate that the amygdala appears to be an important brain structure for the processing of the metaplastic effect of nicotine on cocaine. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'. PMID:23597510

  9. The chronic infusion of nicotine into the developing chick embryo does not alter the density of (-)-[3H]nicotine-binding sites or vestibular function

    NASA Technical Reports Server (NTRS)

    Roll, R. L.; Jones, T. A.; Benowitz, N. L.; Morley, B. J.

    1993-01-01

    (-)-Nicotine (1.2 mg/day) or saline was infused into chick embryos (Gallus domesticus) for 10 days beginning 12 h beyond the eight day of incubation (E8 + 12 h). Twelve h beyond the eighteenth day of incubation (E18 + 12 h), the eggs were opened to access the embryos and subcutaneous skull electrodes placed. Short latency vestibular response thresholds and input/output functions were determined to assess neurophysiological consequences of chronic nicotine administration. Samples of serum and extraembryonic (amniotic and albumen) fluid were analyzed by gas chromatography-mass spectrometry to determine the levels of nicotine and its major metabolite, cotinine. The brains were removed and divided into diencephalon and mesencephalon and the density of (-)-[3H]nicotine binding sites in each brain area was measured. Nicotine and cotinine were found in the serum and extraembryonic fluid, but nicotinic receptors were not up-regulated in the brains of animals infused with nicotine in comparison to controls. Vestibular response thresholds also did not differ between nicotine-treated and control animals.

  10. Beta-cryptoxanthin restores nicotine-reduced lung SIRT1 to normal levels and inhibits nicotine-promoted lung tumorigenesis and emphysema in A/J mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nicotine, a large constituent of cigarette smoke, is associated with an increased risk of lung cancer, but the data supporting this relationship are inconsistent. Here, we found that nicotine treatment not only induced emphysema but also increased both lung tumor multiplicity and volume in 4-nitrosa...

  11. Nicotine and Non-Nicotine Smoking Factors Differentially Modulate Craving, Withdrawal and Cerebral Blood Flow as Measured with Arterial Spin Labeling

    PubMed Central

    Addicott, Merideth A; Froeliger, Brett; Kozink, Rachel V; Van Wert, Dana M; Westman, Eric C; Rose, Jed E; McClernon, Francis J

    2014-01-01

    Smoking cessation results in withdrawal symptoms such as craving and negative mood that may contribute to lapse and relapse. Little is known regarding whether these symptoms are associated with the nicotine or non-nicotine components of cigarette smoke. Using arterial spin labeling, we measured resting-state cerebral blood flow (CBF) in 29 adult smokers across four conditions: (1) nicotine patch+denicotinized cigarette smoking, (2) nicotine patch+abstinence from smoking, (3) placebo patch+denicotinized cigarette smoking, and (4) placebo patch+abstinence from smoking. We found that changes in self-reported craving positively correlated with changes in CBF from the denicotinized cigarette smoking conditions to the abstinent conditions. These correlations were found in several regions throughout the brain. Self-reported craving also increased from the nicotine to the placebo conditions, but had a minimal relationship with changes in CBF. The results of this study suggest that the non-nicotine components of cigarette smoke significantly impact withdrawal symptoms and associated brain areas, independently of the effects of nicotine. As such, the effects of non-nicotine factors are important to consider in the design and development of smoking cessation interventions and tobacco regulation. PMID:24820539

  12. Nicotine and non-nicotine smoking factors differentially modulate craving, withdrawal and cerebral blood flow as measured with arterial spin labeling.

    PubMed

    Addicott, Merideth A; Froeliger, Brett; Kozink, Rachel V; Van Wert, Dana M; Westman, Eric C; Rose, Jed E; McClernon, Francis J

    2014-11-01

    Smoking cessation results in withdrawal symptoms such as craving and negative mood that may contribute to lapse and relapse. Little is known regarding whether these symptoms are associated with the nicotine or non-nicotine components of cigarette smoke. Using arterial spin labeling, we measured resting-state cerebral blood flow (CBF) in 29 adult smokers across four conditions: (1) nicotine patch+denicotinized cigarette smoking, (2) nicotine patch+abstinence from smoking, (3) placebo patch+denicotinized cigarette smoking, and (4) placebo patch+abstinence from smoking. We found that changes in self-reported craving positively correlated with changes in CBF from the denicotinized cigarette smoking conditions to the abstinent conditions. These correlations were found in several regions throughout the brain. Self-reported craving also increased from the nicotine to the placebo conditions, but had a minimal relationship with changes in CBF. The results of this study suggest that the non-nicotine components of cigarette smoke significantly impact withdrawal symptoms and associated brain areas, independently of the effects of nicotine. As such, the effects of non-nicotine factors are important to consider in the design and development of smoking cessation interventions and tobacco regulation. PMID:24820539

  13. Nicotine promotes cell proliferation via {alpha}7-nicotinic acetylcholine receptor and catecholamine-synthesizing enzymes-mediated pathway in human colon adenocarcinoma HT-29 cells

    SciTech Connect

    Wong, Helen Pui Shan; Yu Le; Lam, Emily Kai Yee; Tai, Emily Kin Ki; Wu, William Ka Kei; Cho, Chi Hin . E-mail: chcho@cuhk.edu.hk

    2007-06-15

    Cigarette smoking has been implicated in colon cancer. Nicotine is a major alkaloid in cigarette smoke. In the present study, we showed that nicotine stimulated HT-29 cell proliferation and adrenaline production in a dose-dependent manner. The stimulatory action of nicotine was reversed by atenolol and ICI 118,551, a {beta}{sub 1}- and {beta}{sub 2}-selective antagonist, respectively, suggesting the role of {beta}-adrenoceptors in mediating the action. Nicotine also significantly upregulated the expression of the catecholamine-synthesizing enzymes [tyrosine hydroxylase (TH), dopamine-{beta}-hydroxylase (D{beta}H) and phenylethanolamine N-methyltransferase]. Inhibitor of TH, a rate-limiting enzyme in the catecholamine-biosynthesis pathway, reduced the actions of nicotine on cell proliferation and adrenaline production. Expression of {alpha}7-nicotinic acetylcholine receptor ({alpha}7-nAChR) was demonstrated in HT-29 cells. Methyllycaconitine, an {alpha}7-nAChR antagonist, reversed the stimulatory actions of nicotine on cell proliferation, TH and D{beta}H expression as well as adrenaline production. Taken together, through the action on {alpha}7-nAChR nicotine stimulates HT-29 cell proliferation via the upregulation of the catecholamine-synthesis pathway and ultimately adrenaline production and {beta}-adrenergic activation. These data reveal the contributory role {alpha}7-nAChR and {beta}-adrenoceptors in the tumorigenesis of colon cancer cells and partly elucidate the carcinogenic action of cigarette smoke on colon cancer.

  14. Correlates of individual differences in compensatory nicotine self-administration in rats following a decrease in nicotine unit dose

    PubMed Central

    Harris, Andrew C.; Pentel, Paul R.; LeSage, Mark G.

    2013-01-01

    Rationale The ability of tobacco harm reduction strategies to produce significant reductions in toxin exposure is limited by compensatory increases in smoking behavior. Characterizing factors contributing to the marked individual variability in compensation may be useful for understanding this phenomenon and assessing the feasibility of harm reduction interventions. Objective To use an animal model of human compensatory smoking that involves a decrease in unit dose supporting nicotine self-administration (NSA) to examine potential contributors to individual differences in compensation. Methods Rats were trained for NSA during daily 23 hr sessions at a unit dose of 0.06 mg/kg/inf until responding was stable. The unit dose was then reduced to 0.03 mg/kg/inf for at least 10 sessions. Following reacquisition of NSA at the training dose and extinction, single-dose nicotine pharmacokinetic parameters were determined. Results Decreases in nicotine intake following dose reduction were proportionally less than the decrease in unit dose, indicating partial compensation. Compensatory increases in infusion rates were observed across the course of the 23 hr sessions. The magnitude of compensation differed considerably between rats. Rats exhibiting the highest baseline infusion rates exhibited the lowest levels of compensation. Nicotine pharmacokinetic parameters were not significantly correlated with compensation. Infusion rates immediately returned to pre-reduction levels when baseline conditions were restored. Conclusions These findings provide initial insights into correlates of individual differences in compensation following a reduction in nicotine unit dose. The present assay may be useful for characterizing mechanisms and potential consequences of the marked individual differences in compensatory smoking observed in humans. PMID:19475400

  15. Evaluation of the Nicotinic Acetylcholine Receptor-Associated Proteome at Baseline and Following Nicotine Exposure in Human and Mouse Cortex.

    PubMed

    McClure-Begley, Tristan D; Esterlis, Irina; Stone, Kathryn L; Lam, TuKiet T; Grady, Sharon R; Colangelo, Christopher M; Lindstrom, Jon M; Marks, Michael J; Picciotto, Marina R

    2016-01-01

    Nicotinic acetylcholine receptors (nAChRs) support the initiation and maintenance of smoking, but the long-term changes occurring in the protein complex as a result of smoking and the nicotine in tobacco are not known. Human studies and animal models have also demonstrated that increasing cholinergic tone increases behaviors related to depression, suggesting that the nAChR-associated proteome could be altered in individuals with mood disorders. We therefore immunopurified nAChRs and associated proteins for quantitative proteomic assessment of changes in protein-protein interactions of high-affinity nAChRs containing the β2 subunit (β2*-nAChRs) from either cortex of mice treated with saline or nicotine, or postmortem human temporal cortex tissue from tobacco-exposed and nonexposed individuals, with a further comparison of diagnosed mood disorder to control subjects. We observed significant effects of nicotine exposure on the β2*-nAChR-associated proteome in human and mouse cortex, particularly in the abundance of the nAChR subunits themselves, as well as putative interacting proteins that make up core components of neuronal excitability (Na/K ATPase subunits), presynaptic neurotransmitter release (syntaxins, SNAP25, synaptotagmin), and a member of a known nAChR protein chaperone family (14-3-3ζ). These findings identify candidate-signaling proteins that could mediate changes in cholinergic signaling via nicotine or tobacco use. Further analysis of identified proteins will determine whether these interactions are essential for primary function of nAChRs at presynaptic terminals. The identification of differences in the nAChR-associated proteome and downstream signaling in subjects with various mood disorders may also identify novel etiological mechanisms and reveal new treatment targets. PMID:27559543

  16. Evaluation of the Nicotinic Acetylcholine Receptor-Associated Proteome at Baseline and Following Nicotine Exposure in Human and Mouse Cortex

    PubMed Central

    Esterlis, Irina; Stone, Kathryn L.; Grady, Sharon R.; Lindstrom, Jon M.; Marks, Michael J.

    2016-01-01

    Abstract Nicotinic acetylcholine receptors (nAChRs) support the initiation and maintenance of smoking, but the long-term changes occurring in the protein complex as a result of smoking and the nicotine in tobacco are not known. Human studies and animal models have also demonstrated that increasing cholinergic tone increases behaviors related to depression, suggesting that the nAChR-associated proteome could be altered in individuals with mood disorders. We therefore immunopurified nAChRs and associated proteins for quantitative proteomic assessment of changes in protein–protein interactions of high-affinity nAChRs containing the β2 subunit (β2*-nAChRs) from either cortex of mice treated with saline or nicotine, or postmortem human temporal cortex tissue from tobacco-exposed and nonexposed individuals, with a further comparison of diagnosed mood disorder to control subjects. We observed significant effects of nicotine exposure on the β2*-nAChR-associated proteome in human and mouse cortex, particularly in the abundance of the nAChR subunits themselves, as well as putative interacting proteins that make up core components of neuronal excitability (Na/K ATPase subunits), presynaptic neurotransmitter release (syntaxins, SNAP25, synaptotagmin), and a member of a known nAChR protein chaperone family (14-3-3ζ). These findings identify candidate-signaling proteins that could mediate changes in cholinergic signaling via nicotine or tobacco use. Further analysis of identified proteins will determine whether these interactions are essential for primary function of nAChRs at presynaptic terminals. The identification of differences in the nAChR-associated proteome and downstream signaling in subjects with various mood disorders may also identify novel etiological mechanisms and reveal new treatment targets. PMID:27559543

  17. Preparation of MgH{sub 2} composite with a composition of 40%MgH{sub 2} + 30%LiBH{sub 4} + 30%(2LiBH{sub 4} + MgF{sub 2})

    SciTech Connect

    Hong, Seong-Hyeon; Song, Myoung Youp

    2012-09-15

    Graphical abstract: Hydrogen content vs. desorption time curves for consecutive 1st desorptions of 40 wt%MgH{sub 2} + 30 wt%LiBH{sub 4} + 30 wt%(2LiBH{sub 4} + MgF{sub 2}) at 533–873 K. Highlights: ► Addition of MgF{sub 2} and LiBH{sub 4} with a higher hydrogen storage capacity to MgH{sub 2}. ► Preparation of 40%MgH{sub 2} + 30%LiBH{sub 4} + 30% (2LiBH{sub 4} + MgF{sub 2}) composite. ► Examination of desorption properties of the composite. ► Total desorbed hydrogen quantity for consecutive 1st desorptions of 7.07 wt%. ► Reactions of LiBH{sub 4} → LiH + B + (3/2)H{sub 2}, and 2LiBH{sub 4} + MgF{sub 2} → 2LiF + MgB{sub 2} + 4H{sub 2}. -- Abstract: A mixture of containing two chemical equivalents of lithium borohyride and one equivalent of magnesium fluoride is known to yield hydrogen in an amount of about 7.6 wt% of the mixture when heated to about 150 °C at atmospheric pressure by the following reaction; 2LiBH{sub 4} + MgF{sub 2} = 2LiF + MgB{sub 2} + 4H{sub 2}. In order to increase hydrogen storage capacity of Mg-based materials, a mixture with a composition of 2LiBH{sub 4} + MgF{sub 2} and LiBH{sub 4}with a higher hydrogen storage capacity of 18.4 wt% were added to MgH{sub 2}. MgH{sub 2} composite with a composition of 40 wt%MgH{sub 2} + 30 wt%LiBH{sub 4} + 30 wt%(2LiBH{sub 4} + MgF{sub 2}) was prepared by reactive mechanical grinding. The hydrogen storage properties of the sample were then examined. Hydrogen content vs. desorption time curves for consecutive 1st desorptions of 40 wt%MgH{sub 2} + 30 wt%LiBH{sub 4} + 30 wt%(2LiBH{sub 4} + MgF{sub 2}) at 533–873 K showed that the total desorbed hydrogen quantity for consecutive 1st desorptions is 7.07 wt%.

  18. Validation of a LC-MS/MS Method for Quantifying Urinary Nicotine, Six Nicotine Metabolites and the Minor Tobacco Alkaloids—Anatabine and Anabasine—in Smokers' Urine

    PubMed Central

    McGuffey, James E.; Wei, Binnian; Bernert, John T.; Morrow, John C.; Xia, Baoyun; Wang, Lanqing; Blount, Benjamin C.

    2014-01-01

    Tobacco use is a major contributor to premature morbidity and mortality. The measurement of nicotine and its metabolites in urine is a valuable tool for evaluating nicotine exposure and for nicotine metabolic profiling—i.e., metabolite ratios. In addition, the minor tobacco alkaloids—anabasine and anatabine—can be useful for monitoring compliance in smoking cessation programs that use nicotine replacement therapy. Because of an increasing demand for the measurement of urinary nicotine metabolites, we developed a rapid, low-cost method that uses isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) for simultaneously quantifying nicotine, six nicotine metabolites, and two minor tobacco alkaloids in smokers' urine. This method enzymatically hydrolyzes conjugated nicotine (primarily glucuronides) and its metabolites. We then use acetone pretreatment to precipitate matrix components (endogenous proteins, salts, phospholipids, and exogenous enzyme) that may interfere with LC-MS/MS analysis. Subsequently, analytes (nicotine, cotinine, hydroxycotinine, norcotinine, nornicotine, cotinine N-oxide, nicotine 1′-N-oxide, anatabine, and anabasine) are chromatographically resolved within a cycle time of 13.5 minutes. The optimized assay produces linear responses across the analyte concentrations typically found in urine collected from daily smokers. Because matrix ion suppression may influence accuracy, we include a discussion of conventions employed in this procedure to minimize matrix interferences. Simplicity, low cost, low maintenance combined with high mean metabolite recovery (76–99%), specificity, accuracy (0–10% bias) and reproducibility (2–9% C.V.) make this method ideal for large high through-put studies. PMID:25013964

  19. Discovery of a novel nicotinic receptor antagonist for the treatment of nicotine addiction: 1-(3-picolinium)-12-triethylammonium-dodecane dibromide (TMPD)

    PubMed Central

    Dwoskin, Linda P.; Joyce, B. Matthew; Zheng, Guangrong; Neugebauer, Nichole M.; Manda, Vamshi K.; Lockman, Paul; Papke, Roger L.; Bardo, Michael T.; Crooks, Peter A.

    2007-01-01

    Limitations in efficacy and high relapse rates of currently available smoking cessation agents reveal the need for more efficacious pharmacotherapies. One strategy is to develop subtype-selective nicotinic receptor (nAChR) antagonists that inhibit nicotine-evoked dopamine (DA) release, the primary neurotransmitter involved in nicotine reward. Simple alkylation of the pyridino N-atom converts nicotine from a potent agonist into a potent antagonist. The classical antagonists, hexamethonium and decamethonium, differentiate between peripheral nAChR subtypes. Using a similar approach, we interconnected varying quaternary ammonium moieties with a lipophilic linker to provide N,N′- bis-nicotinium analogs, affording a lead compound, N,N′-dodecyl-1,12-diyl-bis-3-picolinium dibromide (bPiDDB), which inhibited nicotine-evoked DA release and decreased nicotine self-administration. The current work describes a novel compound, 1-(3-picolinium)-12-triethylammonium-dodecane dibromide (TMPD), a hybrid of bPiDDB and decamethonium. TMPD completely inhibited (IC50 = 500 nM) nicotine-evoked DA release from superfused rat striatal slices, suggesting that TMPD acts as a nAChR antagonist at more than one subtype. TMPD (1 μM) inhibited the response to acetylcholine at α3β4, α4β4, α4β2, and α1β1εδ receptors expressed in Xenopus oocytes. TMPD had a 2-fold higher affinity for the blood-brain barrier choline transporter, suggesting that is brain bioavailable. TMPD did not inhibit the hyperactivity in nicotine sensitized rats, but significantly and specifically decreased nicotine self-administration. Together, the results suggest that TMPD may have the ability to reduce the rewarding effect of nicotine with minimal side effects, a pharmacological profile indicative of potential clinical utility for the treatment of tobacco dependence. PMID:17727820

  20. Nicotine Blocks Brain Estrogen Synthase (Aromatase): In Vivo Positron Emission Tomography Studies in Female Baboons

    SciTech Connect

    Biegon, A.; Biegon, A.; Kim, S.-W.; Logan, J.; Hooker, J.M.; Muench, L.; Fowler, J.S.

    2010-01-12

    Cigarette smoking and nicotine have complex effects on human physiology and behavior, including some effects similar to those elicited by inhibition of aromatase, the last enzyme in estrogen biosynthesis. We report the first in vivo primate study to determine whether there is a direct effect of nicotine administration on brain aromatase. Brain aromatase availability was examined with positron emission tomography and the selective aromatase inhibitor [{sup 11}C]vorozole in six baboons before and after exposure to IV nicotine at .015 and .03 mg/kg. Nicotine administration produced significant, dose-dependent reductions in [{sup 11}C]vorozole binding. The amygdala and preoptic area showed the largest reductions. Plasma levels of nicotine and its major metabolite cotinine were similar to those found in cigarette smokers. Nicotine interacts in vivo with primate brain aromatase in regions involved in mood, aggression, and sexual behavior.

  1. Alcohol and nicotine consumption exacerbates choroidal neovascularization by modulating the regulation of complement system

    PubMed Central

    Kaliappan, Sankaranarayanan; Jha, Purushottam; Lyzogubov, Valeriy V.; Tytarenko, Ruslana G.; Bora, Nalini S.; Bora, Puran S.

    2010-01-01

    The objective of the present study was to investigate the effect of alcohol and nicotine consumption on the pathogenesis of choroidal neovascularization (CNV) in rats after laser-photocoagulation. Confocal microscopic analysis demonstrated an increase in CNV complex size in rats fed with alcohol (2.3-fold), nicotine (1.9-fold), and the combination of alcohol and nicotine (2.7-fold) compared with the control groups. Immunohistochemical analysis revealed that alcohol and nicotine consumption increased MAC deposition and VEGF expression in laser spots. Expression of CD59 by RT-PCR and Western blot was drastically reduced in the animals that were fed with alcohol, nicotine and alcohol and nicotine compared to those fed with water alone and this was associated with exacerbation of CNV. PMID:18789935

  2. Insulin signaling genes modulate nicotine-induced behavioral responses in Caenorhabditis elegans.

    PubMed

    Wescott, Seth A; Ronan, Elizabeth A; Xu, X Z Shawn

    2016-02-01

    Insulin signaling has been suggested to modulate nicotine dependence, but the underlying genetic evidence has been lacking. Here, we used the nematode, Caenorhabditis elegans, to investigate whether genetic alterations in the insulin signaling pathway affect behavioral responses to nicotine. For this, we challenged drug-naive C. elegans with an acute dose of nicotine (100 μmol/l) while recording changes in their locomotion speed. Although nicotine treatment stimulated locomotion speed in wild-type C. elegans, the same treatment reduced locomotion speed in mutants defective in insulin signaling. This phenotype could be suppressed by mutations in daf-16, a gene encoding a FOXO transcription factor that acts downstream of insulin signaling. Our data suggest that insulin signaling genes, daf-2, age-1, pdk-1, akt-1, and akt-2, modulate behavioral responses to nicotine in C. elegans, indicating a genetic link between nicotine behavior and insulin signaling. PMID:26317299

  3. Synthesis of 4,4-ditritio-(+)-nicotine: comparative binding and distribution studies with natural enantiomer

    SciTech Connect

    Vincek, W.C.; Martin, B.R.; Aceto, M.D.; Tripathi, H.L.; May, E.L.; Harris, L.S.

    1981-11-01

    The preparation of 4,4-ditritio-(+)-nicotine (Vb) (specific activity 10.3 Ci/mmole)from (+)-nicotine (Ib) via (-) 4,4-dibromocotinine (IIIb) is described. Although Ib is 10-30 times less potent than (-)-nicotine (Ia) in the CNS, its binding affinity for the crude mitochondrial or nuclear fraction of whole rat brain is only three times less than that of Ia. However, distribution studies showed that the maximum brain levels of (-)-(3H) nicotine are nearly twice those of (+)-(3H)-nicotine following administration of a 2-micrograms/kg dose. Binding affinity and disposition of the stereoisomers account for a portion of the pharmacological stereospecificity of nicotine.

  4. Nicotine Deprivation Produces Deficits in Pain Perception that are Moderately Attenuated by Caffeine Consumption.

    PubMed

    Baiamonte, Brandon A; Stickley, Sarah C; Ford, Sarah J

    2016-01-01

    During withdrawal, nicotine users experience aversive withdrawal symptoms, such as increased nociceptive processing, which may be responsible for subsequent use. Smokers often consume more caffeine than non-smokers and the combined effects of these two psychoactive drugs result in an enhanced analgesic effect of nicotine. We examined the effects of caffeine (via coffee consumption) and nicotine withdrawal on pain perception in minimally deprived smokers and non-smokers. Pain threshold and pain tolerance were assessed using a radiant heat stimulus before and 30 minutes after caffeine consumption. Nicotine deprivation (2 hrs) produced increases in pain threshold and decreases in pain tolerance representative of hyperalgesia. When smokers are nicotine deprived, caffeine consumption diminished baseline elevations in pain threshold, but had no effect on pain tolerance. These data suggest that caffeine consumption can dampen deficits in sensory discrimination related to pain during nicotine deprivation by reducing pain threshold to levels representative of non-smoking controls. PMID:27120004

  5. Developing a model of limited-access nicotine consumption in C57Bl/6J mice.

    PubMed

    Kasten, C R; Frazee, A M; Boehm, S L

    2016-09-01

    Although United States smoking rates have been on the decline over the past few decades, cigarette smoking still poses a critical health and economic threat. Very few treatment options for smoking exist, and many of them do not lead to long-term abstinence. Preclinical models are necessary for understanding the effects of nicotine and developing treatments. Current self-administration models of nicotine intake may require surgical procedures and often result in low levels of intake. Further, they do not lend themselves to investigating treatments. The current study sought to develop a limited-access model of nicotine intake using the Drinking-in-the-Dark paradigm, which results in high levels of binge-like ethanol consumption that can be pharmacologically manipulated. The present study found that mice will consume nicotine under a range of parameters. Intakes under the preferred condition of 0.14mg/ml nicotine in 0.2% saccharin reached over 6mg/kg in two hours and were reduced by an injection of R(+)-baclofen. Mecamylamine did not significantly affect nicotine consumption. As nicotine and ethanol are often co-abused, nicotine intake was also tested in the presence of ethanol. When presented in the same bottle, mice altered nicotine intake under various concentrations to maintain consistent levels of ethanol intake. When nicotine and ethanol were presented in separate bottles, mice greatly reduced their nicotine intake while maintaining ethanol intake. In conclusion, these studies characterize a novel model of limited-access nicotine intake that can be pharmacologically manipulated. PMID:27242276

  6. Nicotine attenuates spatial learning deficits induced in the rat by perinatal lead exposure.

    PubMed

    Zhou, Mingfu; Suszkiw, Janusz B

    2004-02-27

    Maternally lead (Pb)-exposed, juvenile rats exhibit significant deficits in spatial reference memory acquisition and working memory performance in the Morris water maze (MWM). Acute systemic application of nicotine reverses these deficits without affecting behavioral performance of the age-matched, lead-unexposed control animals. These results suggest that nicotinic agonist treatments can ameliorate learning and memory impairments, presumably by compensating for deficient nicotinic function in developmentally lead-exposed animals. PMID:14746932

  7. Functional expression of human α7 nicotinic acetylcholine receptor in human embryonic kidney 293 cells.

    PubMed

    Gong, Yuan; Jiang, Ji-Hong; Li, Shi-Tong

    2016-09-01

    The functional expression of recombinant α7 nicotinic acetylcholine receptors in human embryonic kidney (HEK) 293 cells has presented a challenge. Resistance to inhibitors of cholinesterase 3 (RIC‑3) has been confirmed to act as a molecular chaperone of nicotinic acetylcholine receptors. The primary objectives of the present study were to investigate whether the co‑expression of human (h)RIC‑3 with human α7 nicotinic acetylcholine receptor in HEK 293 cells facilitates functional expression of the α7 nicotinic acetylcholine receptor. Subsequent to transfection, western blotting and polymerase chain reaction were used to test the expression of α7 nicotinic acetylcholine receptor and RIC-3. The α7 nicotinic acetylcholine receptor was expressed alone or co‑expressed with hRIC‑3 in the HEK 293 cells. Drug‑containing solution was then applied to the cells via a gravity‑driven perfusion system. Calcium influx in the cells was analyzed using calcium imaging. Nicotine did not induce calcium influx in the HEK 293 cells expressing human α7 nicotinic acetylcholine receptor only. However, in the cells co‑expressing human RIC‑3 and α7 nicotinic acetylcholine receptor, nicotine induced calcium influx via the α7 nicotinic acetylcholine receptor in a concentration‑dependent manner (concentration required to elicit 50% of the maximal effect=29.21 µM). Taken together, the results of the present study suggested that the co‑expression of RIC‑3 in HEK 293 cells facilitated the