Caffeine and nicotine are the two most commonly consumed licit psychoactive drugs in the world. In addition, they are frequently co-administered with over 86% of cigarette smokers reporting caffeine use versus 77% of non-smokers. Research suggests the combination of nicotine and caffeine produces effects that are more rewarding or pleasurable than either drug alone, and this potential reward enhancement may influence patterns of tobacco use initiation and maintenance. Waterpipe tobacco smoking is an alternative tobacco use method that is increasing in prevalence in the U.S. and offers a novel opportunity for nicotine and caffeine co-administration via a caffeinated tobacco product (Tangiers F-Line). Based on previous work, this caffeinated tobacco product was hypothesized to enhance reward-related and cardiovascular effects in waterpipe users relative to tobacco-only waterpipe preparations. Thirty-two waterpipe tobacco smokers who regularly drank caffeinated beverages participated in a four condition, Latin-square ordered, within-subjects study. In each condition, there was a 45-minute double-blind product administration period that differed by the content of waterpipe product smoked: caffeine and nicotine (Tangiers F-Line), nicotine and no caffeine (Tangiers), reduced (low) nicotine and caffeine (low nicotine Tangiers F-Line), or neither nicotine nor caffeine (Soex). Outcome measures included blood plasma caffeine and nicotine, cardiovascular response, expired air carbon monoxide (CO), puff topography, and subjective ratings. Plasma analyses revealed no detectable levels of caffeine from either caffeinated product, but significant nicotine exposure from all nicotine-containing products. Few differences between conditions were observed for subjective measures. Larger puff volumes were observed for products that contained low or no nicotine, resulting in higher CO concentrations for these conditions. While findings do not address whether caffeine can be delivered via volatilization, they suggest that measurable caffeine exposure was not observed for the products examined and under the conditions explored here. Importantly, study results support continued investigation of the effects of waterpipe tobacco smoking using a placebo-controlled design as well as demonstrate that tobacco dependence and toxicity capabilities are still concerns for these and other waterpipe products.

Two proposed models will be used to help answer a long observed question in the dynamics of \textit{Manduca sexta} and its related parasitoid wasps-Why is there a large difference in diversity in hyperparasitoid species between tobacco and other related plants such as tomato? Two stage structured differential equation models are presented. The first is a single patch model to study the changes in dynamics that occur between hosts, parasitoids, and hyperparasitoids as the amount of nicotine in the plant increases. The second is a two patch model that allows hyperparasitoids to choose between patches that are nicotine negative (i.e. tomato plants) and nicotine positive (i.e. tobacco plants). Both models will be used to investigate how host nicotine sequestration may impact hyperparasitoid diversity.

Nicotine is one of the most commonly used drugs among adolescent populations. Given the fact that adolescence is a unique developmental stage, during which nicotine has long-term effects on future drug-taking behavior, it is essential to understand how early exposure to nicotine during adolescence may affect the abuse liability of other drugs. We hypothesize that repeated exposure to low doses of nicotine in adolescence induce age-specific enhancement of the rewarding effects of several drugs of abuse in the conditioned place preference (CPP) test. Furthermore, we predict that these changes in behavioral responses are mediated by nicotine-induced brain region-specific increases in the expression of ΔFosB, a member of the Fos family of transcription factors, through activation of neuronal nicotinic receptors. We used mice as a model system to investigate the effects of adolescent nicotine exposure on responses to cocaine, amphetamine, and morphine in adulthood. We found that exposure to nicotine during the early phase of adolescence (postnatal day 28) enhanced cocaine CPP, acute locomotor activity, and locomotor sensitization in adulthood. Our data demonstrate that nicotine priming effects on cocaine are affected by the dose, duration, method of administration, age of exposure, and mouse strain. These data strongly suggest that nicotine intake during adolescence may cross-sensitize the brain to the rewarding effects of cocaine. A follow-up study was undertaken to determine if this enhancement applies to other drugs of abuse. The repeated exposure to 0.5 mg/kg nicotine (subcutaneous) during early adolescence resulted in significant enhancement of amphetamine and morphine preference in a CPP test, but had no effect on the somatic signs of morphine withdrawal. In addition, we investigated the possible neuronal mechanisms underlining enhancements to behavioral responses using both in vivo and in vitro techniques. Our results showed that nicotinic antagonists, with varying subtype selectivity, administered during adolescence prior to nicotine exposure diminished cocaine enhancement in CPP. This suggests that the enhancement of cocaine behavioral responses is mediated by neuronal nicotine receptors (mainly β2* and α7). Finally, studies of ∆FosB revealed significant effects of age and nicotine pre-treatment in nucleus accumbens (NAc), but not in the prefrontal cortex (PFC). Indeed, nicotine pre-treatment was able to significantly increase ∆FosB levels in NAc of early adolescent mice compared to adult mice. This accumulation of ∆FosB persisted for several weeks. Further studies are needed to fully examine the mechanisms of action underlying the observed changes in cocaine rewards.

Nicotine is one of the first and most commonly abused drugs in adolescence. According to The Center for Disease Control, every day more than 6000 adolescents try their first cigarette and over 3000 of them become daily smokers. Smoking among adolescents is a strong predictor of future drug abuse and dependence in adulthood. A number of studies has suggests that adolescents pre-exposed to nicotine may suffer permanent disruption of the brain’s reward systems through changes in dopamine receptor function. We hypothesize that nicotine exposure during adolescence causes long lasting neurobiological alterations that increase the likelihood of cocaine use in adulthood. Furthermore, it activates a neurobiological mechanism that is shared by many drugs of abuse, which will increase susceptibility to their rewarding effects. The work in this thesis contributes to the further understanding of this critical developmental period. Conditioned-place-preference, acute locomotor and locomotor sensitization pardigms were used to examine changes in cocaine sensitivity in adulthood. Testing was performed on adult ICR mice that were exposed to nicotine (0.1 or 0.5 mg/kg, S.C., b.i.d.) or saline during adolescence (postnatal days 28 or 46) or adult (postnatal day 70). Data showed that a 7-day exposure to the higher dose of nicotine (0.5 mg/kg) altered cocaine-induced responses. In contrast, neither 1 day exposure nor a low dose of nicotine (0.1 mg/kg) elicited this effect. A follow-up study was undertaken to determine if this enhancement generally applies to other drugs of abuse. Pre-exposure to 0.5mg/kg nicotine during early adolescence demonstrated significant enhancement to morphine reward, but it failed to increase d-amphetamine preference in a CPP model. Further research will be required in order to more fully examine the mechanisms of action for the observed changes in cocaine rewards. In summary, these findings suggest that early adolescent nicotine exposure leads to changes in cocaine reward and sensitivity during adulthood in both dose and duration matters. Indeed, the adolescent brain is uniquely vulnerable to the effects of nicotine on subsequent drug reward.

Electronic cigarettes (ECIGs) operate by heating a nicotine-containing solution resulting in an inhalable aerosol. Nicotine delivery may be affected by users’ puffing behavior (puff topography), and little is known about the puff topography of ECIG users. The purpose of this study was to examine the extent to which a mouthpiece-based topography measurement device influences the acute effects associated with ECIG use. Twenty-nine experienced ECIG users completed two sessions differing only by the presence of a mouthpiece-based topography recording device. In both sessions, participants completed one 10 puff, 30 sec inter-puff interval (IPI) ECIG-use bout and another 90 minute ad libitum bout. Acute ECIG effects (plasma nicotine concentration, heart rate [HR], and subjective effects) were largely unaffected by the presence of the topography recording device. Evaluating ECIG puff topography through clinical laboratory methodology is necessary to understand the effects of these products (including toxicant exposure) and to inform their regulation.

In my work I deal with smoking among clients seeking treatment for depression or neurotic disorders. The aim of my work is to examine the relationship between depression, anxiety and addiction to nicotine.The research was conducted through a questionnaire survey among clients of day care centres and psychiatric department. Overall, participated in the research was 32 respondents, including 20 women and 12 men. The average age of respondents was 39 years. 22 respondents completing the questionnaire identified yourself as regular smokers, 2 as occasional, 3 as ex-smokers and 5 respondents as nonsmokers. The research was conducted from December 2012 to April 2013. I found that respondents smoke as well, if they feel mentally well. If they are mentally ill, smoke more. During hospitalization or visits to day care centres smoke as much or more. Depressed and anxious thoughts of the respondents almost always leads to a light taste. The relationship between smoking and depression I was able to prove only in the group of smokers.

Severas altera¸c~oes no metabolismo energ´etico, no consumo de glicose e na sinaliza¸c~ao de insulina cerebral est~ao presentes na doen¸ca de Alzheimer (DA). O modelo animal da DA obtido pela administra¸c~ao intracerebroventricular de estreptozotocina (STZ-icv) em ratos induz um estado de resist^encia `a insulina no c´erebro associado `a disfun¸c~oes colin´ergicas e a d´eficits cognitivos, tornando-o um dos poucos modelos experimentais da forma espor´adica da DA. Este trabalho tem como objetivo caracterizar, neste modelo, as disfun¸c~oes sin´apticas na via hipocampo - c´ortex pr´e-frontal medial (CA1-CPFm) e testar se o tratamento com nicotina ´e capaz de prevenir as disfun¸c~oes sin´apticas e reverter os preju´?zos cognitivos induzido pelo STZ-icv. Para isso, ratos Wistar receberam STZ e foram submetidos a 20 dias de tratamento com nicotina. Dois dias depois, foram realizados nos animais teste de campo aberto e de reconhecimento de objeto. Em seguida os animais foram anestesiados com uretana para que os registros eletrofisiol´ogicos fossem realizados. Um eletrodo foi utilizado para estimular CA1 com pulso pareado e potenciais de campo p´os-sin´apticos (fPSP1) e sua facilita¸c~ao (fPSP2) foram registradas por um eletrodo no CPFm. Ap´os 30 minutos de linha de base, uma estimula¸c~ao em alta frequ^encia foi aplicada para induzir a potencia¸c~ao de longa dura¸c~ao (LTP), seguido de mais quatro horas de registro. Outro grupo experimental foi realizado para avaliar o efeito de longo prazo da STZ-icv e do tratamento com nicotina. Neste grupo, testes comportamentais e eletrofisiol´ogicos foram realizados 60 dias ap´os o fim do tratamento. Independentemente do tempo, os resultados indicam que a STZ produziu uma redu¸c~ao na indu¸c~ao e na manuten¸c~ao da LTP, mas a facilita¸c~ao por pulso pareado (PPF = fPSP2 / fPSP1) mostra que a STZ prejudica a plasticidade pr´e-sin´aptica apenas a curto prazo. O tratamento com nicotina atenua a disfun¸c~ao na LTP induzida pela STZ. Al´em disso, apenas o tratamento de nicotina tamb´em ´e capaz de reduzir a plasticidade pr´e-sin´aptica no grupo controle dois dias ap´os o fim do tratamento. Estes resultados tamb´em est~ao associados com os dados comportamentais, uma vez que a nicotina reverteu os d´eficits de mem´oria de reconhecimento nos animais STZ mas manteve o comportamento explorat´orio reduzido. Sugerimos com isso que o sistema colin´ergico, que desempenha um papel importante em fun¸c~oes cognitivas e na LTP, est´a afetado nos animais injetados com STZ e o tratamento cr^onico com nicotina consegue reduzir os danos na plasticidade sin´aptica e comportamentais, induzidos pela STZ. / Severe abnormalities in brain glucose/energy metabolism and insulin signaling have been documented to play an important role in early stage of alzheimer disease (AD) pathology. Intracerebroventricular administration (icv) of streptozotocin (STZ) in rats can induce an insulin-resistant brain state associated with cholinergic dysfunctions and memory impairments, which make it a suitable experimental model of the sporadic form of AD. The present work aimed to extend the characterization of this model by probing synaptic plasticity dysfunctions in the medial prefrontal cortex (mPFC)- hippocampal (CA1) pathway and test if nicotine can prevent synaptic dysfunction and revert cognitive impairment induced by icv STZ. Here, Wistar rats received bilateral microinjection of STZ and were submitted to 20 days of nicotine treatment. After 2 days of withdrawing the subjects were submitted to open field and object recognition tests. After that, animals were anesthetized with urethane for electrophysiological tests. A twisted bipolar electrode was used to stimulate posterior-dorsal hippocampus (CA1/subiculum) with paired-pulse. Basal field post-synaptic potentials (fPSP1) and facilitated responses (fPSP2) were recorded by a monopolar electrode in the medial mPFC. After 30min of baseline, high frequency stimulation was applied to induce long-term potentiation (LTP) and additional four hours of electrophysiological recordings was performed. Another experimental group was performed to evaluate the long term effect of both icv STZ and nicotine treatment. In this group behavioral and electrophysiological tests were performed with 60 days after chronic treatment. Independently of time, our results indicate that STZ produced a significant decrease in the induction and maintenance of LTP, but paired pulse facilitation (PPF = fPSP2/fPSP1) shows that only the short-term pre-synaptic plasticity was impaired after STZ injection. The nicotine treatment attenuates the STZ-induced LTP dysfunction in the CA1-mPFC pathway. However, just the nicotine treatment (in control group) can reduce pre-synaptic plasticity two days after chronic treatment. These results are also associated with behavioral data, since nicotine treatment reversed the deficits in recognition memory of STZ animals but maintained the reduced exploratory behavior. We suggest that the brain cholinergic system, which plays a role in cognition function and LTP, is affected in STZ injected animals and chronic treatment with nicotine can attenuate the STZ-induced synaptic plasticity and behavioral dysfunctions.

Thesis advisor: Stephen Heinrichs / The present study seeks to use an animal model to examine how dietary restriction, physiological and non-physiological needs, and nicotine administration influence eating behavior. Diets restricting proteins were fed to rats in order to assess if any abnormalities in feeding behavior result. Following a plan of limited access to the restricted nutrient a physiological rebound occurred, involving increased selection for the restricted nutrient. Non-physiological needs were also be studied by observing the effect of taste modification on the eating behavior. The taste of the restricted nutrient was modified to have a preferred, sweet taste or non-preferred, bitter taste. Non-physiological drives to avoid unpleasant tastes were overridden by the physiological need for the restricted nutrient. Furthermore, the drive to increase consumption of a pleasant tasting food was seen only in protein deficient rats, whereas rats that were not deficient in protein ate as much of the sweet tasting food as the unadultered food. Nicotine administration was seen to suppress the physiological need for the deficient nutrient, and withdrawal of nicotine resulted in a return to the normal physiological drive for the restricted nutrient. / Thesis (BA) — Boston College, 2004. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Psychology. / Discipline: College Honors Program.

Pang Wang Kee, Wankie. / Summary in Chinese. / Thesis (M.B.A.)--Chinese University of Hong Kong. / Bibliography: leaves 174-176.

The role of the immune system in periodontal disease has been well established. Individuals who smoke are more prone to developing periodontitis because of the excess plaque buildup and the immune system's attack of the bacteria on the gingiva. This study aims to examine the role of immunotherapy in the reversal of periodontal disease in individuals who smoke. Further research will not only assist with the reversal of periodontitis, but may also improve other debilitating co-morbid diseases including autoimmune diseases such as human immunodeficiency virus. To examine this question, a variety of research studies from various sources were examined. There are numerous factors, which contribute to the initiation and progression of periodontal disease. Use of nicotine products enhances the accumulation of plaque formation. Accumulation of large amounts of plaque and calculus assist in the progression of periodontal disease. Disease of the gingiva may lead numerous other debilitating diseases such as respiratory infections, Alzheimer's disease and unfavorable pregnancy outcomes. Two components of the immune system play a major role in gingival inflammation observed in smokers; these include cytokine production and inflammation. The concentration of pro-inflammatory cytokines released from the macrophages of smokers is significantly higher than that observed in non-smokers. Pro-inflammatory cytokines, such as TNF-alpha, are responsible for inflammation of the gingiva. The use of pre-existing immunotherapy treatments may be beneficial and assist in the reversal of periodontal disease. Further researcher on immune therapy, which has been shown to be successful in other disease treatments will not only be beneficial for the oral cavity, but for overall systemic health. Both immune and bacterial components should be taken into consideration when developing therapies for periodontal disease. Pro-inflammatory cytokines such as TNF-alpha are dramatically increased in smokers. Researchers should model therapies after existing therapies that have been successful for other diseases such as immunotherapy studies with lamvidine (Hepatitis B), lambrolixumab (melanoma) and infliximad (oral plaque). The mTOR signaling pathway controls the release of pro-inflammatory and anti-inflammatory cytokines. Deletion of the raptor protein causes more inflammation in the colon due to an increased release of pro-inflammatory cytokines. Therapies which directly act upon this signaling pathway should be further researched upon to reverse the effects of periodontal disease. Chromogranin A release showed a significant increase in smokers because of the body's ability to want to automatically attach the harsh environment created by tobacco. Modulating the immune response induced by Chromagranin A or possibly through the use of anti-TNF-alpha therapies which have shown success in patients with rheumatoid arthritis also is open to future research. The shift from gram-negative to gram-positive bacteria was noted in periodontal disease patients. The less diverse bacteria lead to the loss of the ability of ligaments to attach to one another in the oral cavity. The development and testing of bacteria specific antibiotics such as Fusobacterium, Prevotella, and Selenomonas may prove to be very beneficial. There is much optimism among the dental professionals that immunotherapy may lead to the development of future therapies for periodontitis in both smokers and non-smokers. However we must also encourage patients to stop smoking through awareness and education.