Thesis (Ph. D.)--Drexel University, 2007. / Includes abstract and vita. Includes bibliographical references (leaves [104-137]).

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 103-121).

abstract: Nicotine is thought to underlie the reinforcing and dependence-producing effects of tobacco-containing products. Nicotine supports self-administration in rodents, although measures of its reinforcing effects are often confounded by procedures that are used to facilitate acquisition, such as food restriction, prior reinforcement training, or response-contingent co-delivery of a naturally reinforcing light. This study examined whether rats acquire nicotine self-administration in the absence of these facilitators. A new mathematical modeling procedure was used to define the criterion for acquisition and to determine dose-dependent differences in rate and asymptote levels of intake. Rats were trained across 20 daily 2-h sessions occurring 6 days/week in chambers equipped with active and inactive levers. Each active lever press resulted in nicotine reinforcement (0, 0.015, 0.03, 0.06 mg/kg, IV) and retraction of both levers for a 20-s time out, whereas inactive lever presses had no consequences. Acquisition was defined by the best fit of a logistic function (i.e., S-shaped) versus a constant function (i.e., flat line) for reinforcers obtained across sessions using a corrected Akaike information criterion (AICc) as a model selection tool. The results showed an inverted-U shaped function for dose in relation to the percentage of animals that acquired nicotine self-administration, with 46% acquiring at 0.015 mg/kg, 73% at 0.03 mg/kg, and 58% at 0.06 mg/kg. All saline rats failed to acquire as expected. For rats that acquired nicotine self-administration, multiple model comparisons demonstrated that the asymptote (highest number of reinforcers/session) and half learning point (h; session during which half the assymptote had been achieved) were justified as free parameters of the reinforcers/session function, indicating that these parameters vary with nicotine dose. Asymptote exhibited an inverted U-shaped function across doses and half learning point exhibited a negative relationship to dose (i.e., the higher the dose the fewer sessions to reach h). These findings suggest that some rats acquire nicotine self-administration without using procedures that confound measures of acquisition rate. Furthermore, the modeling approach provides a new way of defining acquisition of drug self-administration that takes advantage of using all data generated from individual subjects and is less arbitrary than some criteria that are currently used. / Dissertation/Thesis / M.A. Psychology 2011

Nicotine and stimulant medications share similar neurotransmission-related effects in the pre-frontal cortex, but it is unclear if nicotine has a similar benefit on inhibitory control. Impulsivity resulting from deficits in inhibition and sustained attention have been posited as a unifying mechanism of adult ADHD psychopathology. These deficits were quantified in the present study using Go/No-Go task accuracy and intra-individual reaction time variability (RTV). The electro-cortical P3a amplitude indexes inhibitory cognitive processes and sustained attention-related frontal cortex activation in response to infrequent NOGO stimuli. However, little work has characterized the effects of nicotine on P3a or RTV in adult ADHD. Therefore, the effects of the nicotine patch on NOGO P3a amplitude, inhibitory accuracy, and RTV were assessed in non-medicated ADHD adults (12 smokers, 12 never-smokers) in a double-blind, placebo-controlled, repeated-measures design. Nicotine patch, relative to placebo patch, significantly increased NOGO inhibitory accuracy, significantly decreased GO RTV, and significantly increased NOGO P3a peak amplitude at four frontal electrode sites. These results suggest that the nicotine reduces impulsivity in adults with ADHD. The implications of these basic findings to the clinical assessment and treatment of ADHD are discussed. Additional reports at both the basic and clinical levels are needed to confirm and extend these findings.

A growing body of research is targeted towards explaining nicotine's numerous and complex effects on selective attention and other forms of attentional processing. However, when and how nicotine modulates attentional processing in the presence of emotional distractors is not well characterized, though potentially quite important given that, relative to nonsmokers, smokers exhibit higher levels of negative affect-related traits and psychological disorders related to negative affect. In this study, electroencephalography (EEG) and event-related potentials (ERPs) were used to better characterize the effects of nicotine replacement therapy (NRT), relative to placebo, on distraction by emotional and smoking-related stimuli across 17 days of abstinence in dependent smokers. It was hypothesized that, relative to placebo, NRT would reduce ERP-indexed distraction (N170) and promote P3b-indexed task-related attention to target digits during a rapidly visual information processing task previously proven to be sensitive to the effects of NRT on attention. It was expected that the effects of valence on N170 to visual distractors and P3b to target digits would be greater in the placebo group than in the NRT group. Results demonstrated that NRT reduced distraction by visual distractors and increased neuroelectric response to target digits relative to placebo patch. Additionally, analyses revealed that the emotional valence of the visual distractors affected P3b response to targets, but did not affect N170-measured distraction during a sustained attention task. Aspects of the effect of NRT and nicotine-abstinence on top-down and bottom-up processes are discussed as possible mechanisms for the effect of nicotine on attention.

abstract: ADHD is a childhood neurobehavioral disorder characterized by inordinate levels of hyperactivity, inattention and impulsivity. The inability to withhold a reinforced response, or response inhibition capacity (RIC), is one aspect of impulsivity associated with ADHD. The first goal of this dissertation was to evaluate the fixed minimum interval (FMI) schedule as a method for assessing RIC. Chapter 2 showed that latencies were substantially more sensitive than FMI-derived estimates of RIC to the effects of pre-feeding and changes in rate and magnitude of reinforcement. Chapter 3 examined the ability of the FMI to discriminate between spontaneously hypertensive rats (SHR), an animal model of ADHD, and Wistar Kyoto (WKY) controls. Results from Chapter 3 showed that RIC was not substantially different between SHR and WKY rats. However, latencies were significantly shorter for SHRs than for WKYs suggesting incentive motivation differed between strains. The second goal of this dissertation was to examine the sensitivity of the SHR to nicotine. ADHD is a risk factor for tobacco dependence. The goal of Chapters 4 and 5 was to determine whether the SHR provided a model of ADHD-related tobacco sensitivity. Chapter 4 examined nicotine's locomotor and rewarding effects in adolescent SHRs using the conditioned place preference (CPP) procedure. SHRs developed CPP to the highest nicotine dose tested and were sensitive to nicotine's locomotor-enhancing properties. WKY controls did not develop CPP to any nicotine dose tested and were not sensitive to nicotine's locomotor properties. However, it is likely that nicotine effects were obscured by a pseudo-conditioning to saline in WKYs. Chapter 5 demonstrated that SHRs were more active than WKYs in the open-field but not in the Rotorat apparatus. Results also showed that SHRs and WKYs were both sensitive to nicotine's locomotor sensitizing effects. However, WKYs were more sensitive than SHRs to nicotine's locomotor suppressing effects. Collectively, results from Chapters 4 and 5 show that SHRs are sensitive to the rewarding and locomotor-enhancing properties of nicotine. However, more research is necessary to confirm that SHRs are a suitable model for studying ADHD-related tobacco use. / Dissertation/Thesis / Doctoral Dissertation Psychology 2015

Orientador: Cleopatra da Silva Planeta / Banca: Azair Liane Matos do Canto de Souza / Banca: Carlos César Crestani / Banca: Mirtes Costa / Banca: Marcelo Tadeu Marin / Resumo: O estresse, atualmente, é considerado um fator importante na fisiopatologia de muitos distúrbios psiquiátricos. Embora os efeitos do estresse agudo possam ser contrabalanceados por respostas adaptativas, o estresse intenso, repetido ou prolongado pode eliciar alterações neuronais duradouras que constituirão as bases de doenças psiquiátricas, como a depressão. Levantamentos epidemiológicos também mostram elevada prevalência de tabagistas entre pacientes com depressão maior. Estas altas taxas de comorbidade sugerem uma provável relação causal: pacientes com depressão proeminente procurariam a nicotina para alívio dos sintomas. Assim, este trabalho investigou as alterações neuroquímicas e neuroendócrinas mediadas pela nicotina na resposta de adaptação ao estresse, utilizando-se, para tanto, o teste modificado da natação forçada (TNF). Para tanto, ratos Wistar machos foram submetidos ao TNF (30 cm de água, 24 ± 1ºC) por 15 min e tratados (1, 19 e 23h) com nicotina (NIC: 0,5 mg/kg, sc), imipramina (IMI: 15 mg/kg, ip) ou salina (SAL). Uma hora após a última injeção, os animais foram reexpostos (5 min) à mesma cuba. Imediatamente após o teste, os animais foram sacrificados; o hipocampo dorsal (HD) e ventral (HV), hipotálamo (HT) e os núcleos dorsal (DR) e mediano (MR) da rafe foram coletados por punch para quantificação de 5-HT, 5-HIAA e NA por HPLC e o sangue, para quantificação da corticosterona plasmática por radioimunoensaio. O hipocampo total também foi utilizado para avaliar a expressão do receptor serotoninérgico 5-HT1A e do glicorreceptor (GR) por western blot. Ainda, avaliou-se o efeito da prazosina nas alterações neuroquímicas induzidas pelo TNF. O tratamento subcrônico com NIC e IMI reduziu em 39% e 50%, respectivamente, o parâmetro de imobilidade e aumentou em 52% e 66%, respectivamente, as contagens de escalada, em relação ao grupo... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Stress is considered a key component in the pathophysiology of several psychiatric diseases. Although the effects of acute stress can be counterbalanced by adaptative responses, intense, repeated or prolonged stress can elicit long lasting neuronal alterations that are related to the occurrence of psychiatric disorders, such as depression. Epidemiological studies have also identified a high prevalence of smokers among depressive patients. These observations suggest a causal relationship: smoking is a self-medication effort to alleviate some symptoms of depression by nicotine. Then, this study investigated nicotine mediatedneurochemical and neuroendocrine alterations in the adaptation response to stress. The modified forced swmming test (FST), a protocol originally employed for screnning new antidepressant drugs, was employed. Male Wistar rats were placed individually into a container (30-cm of water, 24±1ºC, 15 min - pretest). Then animals received nicotine (0.5 mg/kg, s.c.), imipramine (15 mg/kg, i.p.) or saline injections at 1, 19 and 23h after the pretest. One hour after the injections, animals were placed in the same container for 5 min. Immediately after, the animals were sacrificed; dorsal (DH) and ventral (VH) hippocampus, hypothalamus (HT) and dorsal (DR) and median (MR) raphe nuclei were collected by punch for measurement of 5-HT, 5-HIAA and NA by HPLC (expressed in ng/mg tissue). Blood samples were collected for determination of plasma corticosterone levels by radioimmunoassay. The whole hippocampus was also used to evaluate the expression of the 5-HT1A serotoninergic receptor and glucocorticoid receptor by western blot. The effects of prazosin in TNF induced-neurochemical alterations was also evaluated. Nicotine and imipramine decreased in 39% and 50%, respectively, the immobility behavior and increased in 52% and 66%, respectively, the climbing scores, in relation to saline... (Complete abstract click electronic access below) / Doutor

Made available in DSpace on 2014-06-11T19:28:02Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-08-18Bitstream added on 2014-06-13T20:57:34Z : No. of bitstreams: 1 moraes_ro_me_araca.pdf: 3762007 bytes, checksum: 9c2ec9715d0b3a85fbf41e3f7be91181 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Introdução: A nicotina, uma das drogas mais nocivas a saúde, causa, entre outros fatores, morbidade do enxerto ósseo e compromete a cicatrização óssea. Por outro lado, o tratamento com laser em baixa intensidade pode proporcionar efeitos bioestimulantes, aumentando a microcirculação sanguínea da área irradiada e estimulando fibroblastos, promovendo melhores condições de cicatrização. O objetivo do presente estudo foi analisar a influência do laser em baixa intensidade sobre o processo de reparo de enxertos ósseos autógenos em bloco instalados em animais modificados sistemicamente pelos efeitos indesejáveis da nicotina. Materiais e Métodos: Foram utilizados 72 ratos (Wistar) divididos em Grupo A (n=36), subgrupos GI e GII, submetidos à aplicação de nicotina e Grupo B (n=36), subgrupos GIII e GIV, submetidos à aplicação de solução fisiológica. Transcorridos 30 dias das aplicações, todos animais receberam enxerto ósseo autógeno na mandíbula, tendo como área doadora o osso parietal da calvária, sendo que os animais pertencentes aos subgrupos GII e GIV, receberam o tratamento com laser em baixa intensidade na interface enxerto-leito receptor. Os animais de cada grupo foram submetidos à eutanásia aos 7, 14 e 28 dias pós cirurgia de enxerto. Após o processamento laboratorial de rotina foi realizada a análise histomorfométrica, visando analisar qualitativamente e quantitativamente as etapas presentes nesse processo de reparo ósseo. Resultados: A análise histológica revelou que o grupo nicotina apresentou um atraso da atividade osteogênica na interface enxerto-leito receptor, como também menor organização do tecido de granulação em substituição ao coágulo sanguineo. Contudo, a irradiação do tecido com laser em baixa intensidade proporcionou melhor reparo ósseo. Histometricamente, os subgrupos submetidos à irradiação laser... / Background: The nicotine is one of the mostly drugs more harmful to the health cause, among other factors, morbidity of bone graft and compromises bone healing. Furthermore, treatment with low level laser can provide biostimulation effects, increasing the blood microcirculation in the irradiated area and stimulating fibroblasts promoting better healing. The aim of this study was to evaluate the influence of low level laser therapy on the healing process of autogenous bone grafts installed in block in systemic modificated animals by undesirable effects of nicotine. Methods: Were used 72 rats (Wistar) divided into Group A (n = 36) subgroups GI and GII, submitted to the application of nicotine and Group B (n = 36) subgroups GIII and GIV, submitted to the application of saline solution. After 30 days of applications, all animals received autogenous bone block graft stabilized on mandible, with the parietal bone donor area of the skull, and the animals belonging to subgroups GII and GIV received treatment with low level laser in the bed-graft interface. The animals in each group were euthanized at 7, 14 and 28 days after bone graft surgery. After routine processing was performed histomorphometric analysis in order to analyze qualitatively and quantitatively the timing sequence of bone repair. Results: The histological analysis revealed that the nicotine group showed a delay of osteogenic activity in the bed-graft interface, as well as decreased organization of granulation tissue replacing the blood clot. However, the low level laser irradiation showed better bone healing. Histometrically, the laser subgroups (GII and GIV) demonstrated greater bone formation compared with the respective subgroups (GI and GIII), with significantly statistically results (P˂0) at 14 days (GI 14,27% ± 2,22% versus GII 24,37% ± 11,93% and GIII 24,94% ± 13,06% versus ...(Complete abstract click electronic access below)

Made available in DSpace on 2014-06-11T19:22:49Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-12-14Bitstream added on 2014-06-13T20:47:32Z : No. of bitstreams: 1 xavier_rf_me_prud.pdf: 788260 bytes, checksum: 7ab87eb37bf3e7b481df9e653a6f0f74 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Introdução: A exposição ao cigarro promove alterações que prejudicam a eficácia do transporte mucociliar. Contudo, a influência da intensidade de exposição, assim como os efeitos da abstinência ao tabagismo sobre essas alterações foram pouco elucidados. Objetivos: Avaliar a influência de diferentes intensidades de exposição ao cigarro sobre o transporte mucociliar e o efeito da cessação do tabagismo sobre o transporte mucociliar nasal em fumantes avaliados durante um período de 180 dias. Casuística e Métodos: Participantes de um programa de cessação ao tabagismo, foram avaliados quanto ao histórico tabagístico, ao nível de dependência à nicotina, à avaliação da função pulmonar (espirometria), a concentração de monóxido de carbono no ar exalado (COex), ao nível de carboxihemoglobina (COHb) e ao transporte mucociliar (tempo de trânsito de sacarina – TTS). Para comparação foi avaliado um grupo... / Introduction: Exposure to cigarette smoke promotes changes that harm the effectiveness of the mucociliary clearance. However, the influence of the intensity of exposure, as well as the effects of abstinence from smoking on these changes is poorly understood. Objectives: To assess the influence of different intensities of exposure to cigarette smoke on mucociliary clearance and the effect of cessation of smoking on nasal mucociliary clearance in smokers evaluated over a period of 180 days. Methods: Participants from a smoking cessation programme, were evaluated about smoking behavior, level of nicotine dependence, lung function (spirometry), the carbon monoxide in exhaled air (exhaled CO), the carboxyhemoglobin (COHb) and mucociliary clearance (saccharin transit time - STT). Was evaluated for comparison... (Complete abstract click electronic access below)

Class of 2012 Abstract / Specific Aims: The goal of this project was to evaluate the use of a preparation of the brainstem and spinal cord of neonatal rats that has been widely used for observing and quantifying central nervous activity, as well as the response to pharmacological manipulation. To achieve this, we specifically aimed to remove the intact brainstem and spinal cord of newborn rats, and develop a preparation that would maintain physiological function and allow for recording of electrical activity. Methods: Multiple dissections were performed on neonatal rats. Conditions during the dissections were controlled to maintain physiological function. Once removed, the intact brainstem and spinal cord was placed in a preparation that allowed for manipulation and access to nerve rootlets. Finally, glass suction electrodes were used to record electrical activity directly from the nerve rootlets. Once recorded, the data were stored on a hard drive for further analysis. Main Results: We were successful in isolating the intact brainstem and spinal cord in neonatal rats while maintaining physiological conditions and nervous activity. The preparation allowed for easy access to nerve roots as well as customization for different experiments. We were also successful in recording nerve activity in the preparation and collection of data for use in future experiments Conclusions: We conclude that the brainstem spinal cord preparation described in this study is a valuable tool that allows for recording and analysis of nerve activity, and specifically for measurement of respiratory motor output. This is a preparation that can be used in a variety of experiments that attempt to observe or quantify the activity of central nerve cells and allows for pharmacological interventions that could be applied in various experiments.