The purpose of this study was to investigate the prevalence of smoke-free environment polices throughout the Commonwealth of Virginia at worksites employing fifty or more workers. Specifically, this study assessed policy prevalence, development, implementation, and enforcement. In addition, this study assessed smoke-free environment policy effectiveness. The population for this investigation consisted of telephone surveys of 374 worksites located throughout the Commonwealth of Virginia. Of these worksites, 340 (91%) completed the telephone survey. The population (n = 340) was spread throughout five health regions, Northern, Northwest, Central, Southwest, and East. Descriptive analysis and One-way Analysis of Variance (ANOVA) were applied to investigate differences between these five health regions. An alpha of .05 was selected for this study. Based on the findings, the following conclusions were drawn: (1) Fifty-percent of the worksites located throughout the Commonwealth of Virginia have some form of smoke-free environment policies; (2) The smoke-free environment policy constructs used in the telephone survey guide were statistically significant in identifying differences between the five health regions; (3) Smoke-free environment policies at the worksite are dependent upon health region; (4) Implementation of smoke-free environment policies is dependent upon health region; (5) Enforcement of smoke-free environment policies is dependent upon health region, and (6) Effectiveness of smoke-free environment policies is dependent upon health region. The following recommendations were suggested: (1) Further studies assessing smoke-free environment policy enforcement should be conducted annually; (2) Studies incorporating a qualitative research methodology regarding smoke-free environment policy prevalence should be conducted; (3) Studies involving common smoke-free environment policies at different states should be investigated, and (4) Additional in-depth surveys should be conducted to evaluate health outcomes associated with the implementation of smoke-free environment policies. / Ph. D.

Environmental tobacco smoke (ETS) has been well established as a danger to children. Exposure to secondhand smoke can cause coughing and wheezing, bronchitis, pneumonia, ear infections, asthma, and sudden infant death syndrome (SIDS). Childhood exposure to ETS may also increase the risk of developing leukemia and lymphoma in childhood (Mitchell, 1997) as well as developing lung cancer as an adult (Glantz, 1992). Despite the great strides recently made in the implementation of regulatory measures to safeguard children from ETS in public places like schools, there remains significant concern regarding children's exposure at home and in their out-of-home care facilities (Ashley and Ferrence, 1998, Jarvis, 2000). In 1996, the Centers for Disease Control and Prevention estimated that there were 336,749 Virginia youth exposed to ETS in the home (State Tobacco Control Highlights, 1999). The purpose of this study was to ascertain the number of family day home providers who allow smoking in their home and/or those that have some type of smoking policy. The sample consisted of 746 licensed, registered or locally approved family day home providers through the Department of Social Services. Of these childcare providers, 81.5% (n=608) completed a questionnaire about their tobacco use policy and its effects. An overwhelming majority (94.7%) of providers reported having a tobacco use policy in their family day home. Most of the providers, 67.6% indicated that smoking was allowed outdoors only while 26.3% noted that smoking was not allowed anywhere at any time, indoor or outdoor. Other policy specifics and background information are discussed in the study. The implications of these findings and recommendations for future training and educational programs for family day home providers are also reviewed. / Master of Science

Despite extensive research, the mechanisms behind cardiovascular effects of subchronic environmental tobacco smoke (ETS) remain unclear, but may be related to ETS-induced inflammation and oxidative stress. Additionally, the protective role of resveratrol (RES), a natural antioxidant available in red grapes, is controversial. We hypothesized that the polycyclic aromatic hydrocarbon (PAH) component of ETS is responsible for causing adverse cardiovascular effects. We also hypothesized that the administration of RES is protective against the adverse cardiovascular effects of ETS. In order to address these hypotheses, male juvenile pigs (4-weeks old) were exposed to ETS or ambient air for 28 consecutive days (1 hr/day) and effects compared to 7 days of i.v. injection of the PAH, benzo-a-pyrene (BAP; 5 mg/kg daily). In another experiment, pigs were sham-exposed or ETS-exposed, with or without oral RES treatment (5mg/kg daily). In all experiments, endothelial and left ventricular function were assessed by flow mediated dilation (FMD), and echocardiography, respectively, while blood pressure was evaluated by oscillometry. At the termination of each experiment, serum nitrotyrosine, total nitrate/nitrite (NOx) and C-reactive protein (CRP) were measured as well as hepatic and pulmonary ethoxyresorufin-o-deethylase (EROD) activity to indicate cytochrome P450 1A1 (CYP1A1) expression. Finally, the correlation between pulmonary inflammation and adverse cardiovascular effects was investigated by measuring total and differential white blood cell (WBC) count as well as leukocyte elastase activity in bronchoalveolar lavage fluid at the termination of each experiment. ETS exposure, but not BAP treatment, resulted in a significant impairment of FMD (P<0.0001) and increased left ventricular end diastolic volume (P=0.0032). Cotreatment with RES failed to restore the ETS induced impairment of FMD (P>0.05). However, a trend pointing to an increase in ejection fraction (EF) was noted (P=0.072). ETS, BAP and RES treatments failed to have any effect on blood pressure (P>0.05). BAP injection caused a significant increase in serum nitrotyrosine (P=0.0146) and CRP (P=0.012), but not serum NOx levels (P>0.05). In contrast, ETS exposure resulted in a significant increase in CRP serum levels (P=0.0092), a trend pointing to increased serum nitrotyrosine (P=0.105), and no change in serum NOx levels (P>0.05). The increased nitrotyrosine and CRP with ETS exposure was not reversed by RES administration (P>0.05). ETS exposure increased EROD activity in the lung (P=0.0093), but not the liver (P=0.12). In contrast, BAP treatment had the opposite effect (lung EROD: P=0.621, liver EROD: P=0.01), while RES administration had no effect (P>0.05). ETS exposure (P=0.0139), but not BAP treatment (P=0.723), resulted in increased WBC count in BAL fluid which was not affected by RES administration (P>0.05). These results show that ETS exposure causes lung inflammation, systemic inflammation, oxidative stress-mediated inactivation of nitric oxide and impaired endothelial function. In contrast, BAP failed to alter endothelial function, downstream of the lung, despite systemic inflammation and increased oxidative stress. Furthermore, RES failed to restore endothelial function, or decrease systemic inflammation and oxidative stress. Taken together, these results suggest either that pulmonary inflammatory responses or pulmonary increases in CYP1A1 activity may be more important links to endothelial dysfunction than systemic inflammation and nitric oxide bioactivity. The beneficial effects of RES by itself are manifested only at the cardiac level by improving the ejection fraction, but the work in this thesis failed to detect any ability of RES to ameliorate ETS cardiovascular effects.

This study explored how cultural heritage might affect peoples beliefs, attitudes, and behaviors toward Environmental Tobacco Smoke (ETS), which in turn affected actual ETS exposure. It used data from the 2001 National Survey on Environmental Tobacco Smoke in the Home. It compared two cultural groups: Francophones and the rest of the Canadian population (RCP), and found that Francophone nonsmokers had a significantly higher ETS exposure than the RCP (19.3% vs. 8.5%). The difference was much greater than the difference in smoking prevalence for the two groups (26.2% vs. 22.4%). </p>The study found Francophones scored lower than the RCP in almost every aspect of ETS-related beliefs, attitudes, and behaviors. They were less likely to believe ETS to be harmful and less supportive of ETS-control policies. They were less likely to have done something that reduced ETS exposure at home. In both cultural groups, smokers scored lower than nonsmokers in ETS-related beliefs and attitudes. However, the difference between the two groups remained significant even if the comparisons were done within smokers and nonsmokers. </p>The most significant finding of the study was that Francophones were more likely to trust those so-called ETS-reduction strategies that appeared to be effective but were not in reality (e.g., opening the window when someone smokes). Moreover, there was a statistically significant interaction between smoking status and cultural heritage: fewer nonsmokers than smokers within each cultural group believed that these strategies were really effective, but the difference between the nonsmokers and smokers was significantly smaller for Francophones than that for the RCP. Therefore, the tendency to trust ineffective ETS-reduction strategies, especially among the nonsmokers, explained why Francophones were significantly less likely to adopt strategies that would actually reduce ETS exposure. </p>These results suggest that in order to move ETS policies forward and to effectively reduce ETS exposure among Canadian nonsmokers, the key strategy is to mobilize the nonsmokers to be less tolerant of ETS and more persistent in only allowing smoking to occur outdoors. This will not only help protect nonsmokers from the harm of ETS, but will eventually help smokers to quit smoking.

This study explored how cultural heritage might affect peoples beliefs, attitudes, and behaviors toward Environmental Tobacco Smoke (ETS), which in turn affected actual ETS exposure. It used data from the 2001 National Survey on Environmental Tobacco Smoke in the Home. It compared two cultural groups: Francophones and the rest of the Canadian population (RCP), and found that Francophone nonsmokers had a significantly higher ETS exposure than the RCP (19.3% vs. 8.5%). The difference was much greater than the difference in smoking prevalence for the two groups (26.2% vs. 22.4%). </p>The study found Francophones scored lower than the RCP in almost every aspect of ETS-related beliefs, attitudes, and behaviors. They were less likely to believe ETS to be harmful and less supportive of ETS-control policies. They were less likely to have done something that reduced ETS exposure at home. In both cultural groups, smokers scored lower than nonsmokers in ETS-related beliefs and attitudes. However, the difference between the two groups remained significant even if the comparisons were done within smokers and nonsmokers. </p>The most significant finding of the study was that Francophones were more likely to trust those so-called ETS-reduction strategies that appeared to be effective but were not in reality (e.g., opening the window when someone smokes). Moreover, there was a statistically significant interaction between smoking status and cultural heritage: fewer nonsmokers than smokers within each cultural group believed that these strategies were really effective, but the difference between the nonsmokers and smokers was significantly smaller for Francophones than that for the RCP. Therefore, the tendency to trust ineffective ETS-reduction strategies, especially among the nonsmokers, explained why Francophones were significantly less likely to adopt strategies that would actually reduce ETS exposure. </p>These results suggest that in order to move ETS policies forward and to effectively reduce ETS exposure among Canadian nonsmokers, the key strategy is to mobilize the nonsmokers to be less tolerant of ETS and more persistent in only allowing smoking to occur outdoors. This will not only help protect nonsmokers from the harm of ETS, but will eventually help smokers to quit smoking.

Despite extensive research, the mechanisms behind cardiovascular effects of subchronic environmental tobacco smoke (ETS) remain unclear, but may be related to ETS-induced inflammation and oxidative stress. Additionally, the protective role of resveratrol (RES), a natural antioxidant available in red grapes, is controversial. We hypothesized that the polycyclic aromatic hydrocarbon (PAH) component of ETS is responsible for causing adverse cardiovascular effects. We also hypothesized that the administration of RES is protective against the adverse cardiovascular effects of ETS. In order to address these hypotheses, male juvenile pigs (4-weeks old) were exposed to ETS or ambient air for 28 consecutive days (1 hr/day) and effects compared to 7 days of i.v. injection of the PAH, benzo-a-pyrene (BAP; 5 mg/kg daily). In another experiment, pigs were sham-exposed or ETS-exposed, with or without oral RES treatment (5mg/kg daily). In all experiments, endothelial and left ventricular function were assessed by flow mediated dilation (FMD), and echocardiography, respectively, while blood pressure was evaluated by oscillometry. At the termination of each experiment, serum nitrotyrosine, total nitrate/nitrite (NOx) and C-reactive protein (CRP) were measured as well as hepatic and pulmonary ethoxyresorufin-o-deethylase (EROD) activity to indicate cytochrome P450 1A1 (CYP1A1) expression. Finally, the correlation between pulmonary inflammation and adverse cardiovascular effects was investigated by measuring total and differential white blood cell (WBC) count as well as leukocyte elastase activity in bronchoalveolar lavage fluid at the termination of each experiment. ETS exposure, but not BAP treatment, resulted in a significant impairment of FMD (P<0.0001) and increased left ventricular end diastolic volume (P=0.0032). Cotreatment with RES failed to restore the ETS induced impairment of FMD (P>0.05). However, a trend pointing to an increase in ejection fraction (EF) was noted (P=0.072). ETS, BAP and RES treatments failed to have any effect on blood pressure (P>0.05). BAP injection caused a significant increase in serum nitrotyrosine (P=0.0146) and CRP (P=0.012), but not serum NOx levels (P>0.05). In contrast, ETS exposure resulted in a significant increase in CRP serum levels (P=0.0092), a trend pointing to increased serum nitrotyrosine (P=0.105), and no change in serum NOx levels (P>0.05). The increased nitrotyrosine and CRP with ETS exposure was not reversed by RES administration (P>0.05). ETS exposure increased EROD activity in the lung (P=0.0093), but not the liver (P=0.12). In contrast, BAP treatment had the opposite effect (lung EROD: P=0.621, liver EROD: P=0.01), while RES administration had no effect (P>0.05). ETS exposure (P=0.0139), but not BAP treatment (P=0.723), resulted in increased WBC count in BAL fluid which was not affected by RES administration (P>0.05). These results show that ETS exposure causes lung inflammation, systemic inflammation, oxidative stress-mediated inactivation of nitric oxide and impaired endothelial function. In contrast, BAP failed to alter endothelial function, downstream of the lung, despite systemic inflammation and increased oxidative stress. Furthermore, RES failed to restore endothelial function, or decrease systemic inflammation and oxidative stress. Taken together, these results suggest either that pulmonary inflammatory responses or pulmonary increases in CYP1A1 activity may be more important links to endothelial dysfunction than systemic inflammation and nitric oxide bioactivity. The beneficial effects of RES by itself are manifested only at the cardiac level by improving the ejection fraction, but the work in this thesis failed to detect any ability of RES to ameliorate ETS cardiovascular effects.

Research Doctorate - Doctor of Philosophy (PhD) / Airway inflammation is a key feature of asthma. Currently, airway inflammation can be detected through both invasive and non- invasive methods. Non invasive methods are safe, feasible and a potentially useful way to assess airway inflammatory markers in both healthy children and children with asthma. In this thesis, a variety of non-invasive markers (induced sputum, exhaled nitric oxide, and exhaled breath condensate) was used to investigate childhood asthma. The aim of the first study was to compare and contrast the different airway markers between healthy children and children with asthma. The second study described the different airway inflammatory phenotypes in children with asthma, and examined clinical predictors of these phenotypes; whereas the third study investigated the effects of environmental tobacco smoke (ETS) exposure on airway inflammation in childhood asthma. The final study assessed the knowledge and attitudes of parents of children with asthma towards passive smoking. The studies used both cross- sectional and longitudinal designs. Children with stable asthma aged between 7 - 17 years underwent clinical assessment, spirometry, exhaled nitric oxide (FeNO), exhaled breath condensate and sputum induction. Urinary cotinine was assayed to assess tobacco smoke exposure. These studies have found that children with asthma show differences in both clinical pattern and pathological pattern compared to healthy children. These differences were apparent with elevated FeNO and sputum eosinophils. In children with asthma, there was heterogeneity of airway inflammation. There were 2 stable inflammatory patterns: eosinophilic asthma and paucigranulocytic asthma. Unlike adult asthma, these phenotypes have different clinical features, which may facilitate detection of the phenotypes in clinical practice. ETS exposure in children with asthma was common and associated with a non- eosinophilic pattern of airway inflammation. In children who had a change in ETS exposure, sputum eosinophils were decreased whereas sputum neutrophils were increased during ETS exposure compared to a non- ETS exposure period. Fractional exhaled nitric oxide levels were decreased after exposure to ETS compared to those at the time of non- ETS exposure. The severity of asthma was increased in children living with parents who smoked. As a result, parents of children with asthma, especially smoking parents should be more aware about the harmful effects of smoking on their children’s health and themselves. Health risk awareness about tobacco smoke helps parental smokers alter their smoking behavior as well as protecting children from ETS exposure. In conclusion, the important findings of this thesis are the description of the inflammatory phenotypes in childhood asthma, the identification of clinical predictors of these phenotypes and the determination of the effects of ETS exposure on airway inflammatory patterns in childhood asthma. These results should facilitate understanding and management of childhood asthma and prompt treatment studies based on markers of airway inflammation.

No description available.

Background A significant proportion of children are exposed to environmental tobacco smoke (ETS) throughout the world. This is mainly because of exposure to parental smoking. It is unknown to what extent the negative effects of ETS on respiratory symptoms track from childhood into adulthood. Methods TESAOD (Tucson Epidemiologic Study of Airway Obstructive Disease) is a large population-based prospective study that was initiated in 1972. Participants were followed prospectively with questionnaires and pulmonary function tests (PFTs) completed about every two years in 12 follow-up surveys up to 1996. Skin prick tests and blood samples for IgE measurements were collected at surveys 1, 6, and 11. We identified subjects who entered the study as children (<15 years old) and were followed to adulthood (>18 years) during the study follow-up. Based on questionnaire data, active asthma, wheeze, cough, and chronic cough (cough for three consecutive months) were coded as never (never reported in childhood or adulthood), incident (never reported in childhood, but ≥ one positive report in adulthood), remittent (≥ one positive report in childhood, but not in adulthood), and persistent (≥ one positive report both in childhood and adulthood). PFTs measurements included forced expiratory volume in 1 second, forced vital capacity, and forced expiratory flow at 25-75%. Parent information on smoking status was collected simultaneously at child visits. ETS exposure status was assessed as “ever” or “never” between birth and 15 years. Results Information on parental ETS exposure in childhood and outcomes in adulthood was available for 444 non-Hispanic white participants (51.4% male) with mean age at initial survey of 7.7 years. Total mean follow-up time was 19.0 years (8.8 years in adulthood). Between birth and 15 years, 53.4% of children were exposed to ETS. After adjusting for sex, age at enrollment, years of follow-up, and personal smoking status (assessed at age 15 and above), combined parental ETS exposure in childhood was significantly associated with persistent wheeze (RR(adj) 1.9, p=0.026), persistent cough (RR(adj) 5.9, p<0.001), and persistent (RR(adj) 3.7, p=0.030) and incident chronic cough (RR(adj) 2.3, p=0.040). Paternal ETS exposure in childhood was associated with persistent wheeze (RR(adj) 2.3, p=0.002), persistent cough (RR(adj) 3.9, p<0.001), persistent (RR(adj) 4.8, p=0.004) and incident chronic cough (RR(adj) 2.2, p=0.031), and persistent asthma (RR(adj) 2.3, p=0.016). Maternal ETS exposure was associated with persistent (RR(adj) 1.9, p=0.029) and incident cough (RR(adj) 2.5, p=0.006). Maternal ETS exposure was associated with an increased percent predicted FVC in adulthood (coefficient, 3.75; p=0.019). No other effects on lung function were seen. There were no effects of ETS exposure on total serum IgE or allergic sensitization. ETS exposure was associated with respiratory symptoms in adulthood among both never and current smokers. Conclusions ETS exposure in childhood has long term health effects on lung function and respiratory symptoms. These effects do not appear to be IgE-mediated. ETS exposure, especially paternal ETS exposure, seems to influence the persistence of respiratory symptoms from childhood to adulthood and to affect women more than men. These effects are independent of personal smoking and also seen in never smokers. Both smoking mothers and fathers should be targeted when attempting to reduce ETS exposure among children.

O desenvolvimento encefálico representa um período de grande vulnerabilidade. Embora diversos trabalhos mostrem que a exposição ao fumo passivo pode levar ao desenvolvimento de sintomas psicocomportamentais da farmacodependência, ainda não está claro se a exposição à poluição tabagística ambiental (PTA) na fase inicial de formação do SNC pode levar à predisposição ao uso de drogas de abuso na adolescência. Assim, o foco deste estudo foi avaliar se a exposição à PTA no início do período pós-natal (P) contribui para a sensibilização comportamental e efeitos recompensadores ao etanol e à cocaína durante a adolescência. Camundongos machos Swiss-Webster foram expostos do 3º (P3) ao 15º (P15) dia de vida pós-natal, duas vezes por dia, à mistura da fumaça central e lateral de cigarros referência (3R4F). Na adolescência (P34-P45), foram avaliados os efeitos do tratamento repetido de etanol e cocaína (primeiro protocolo) como também o efeito do tratamento agudo com cocaína (segundo protocolo). No primeiro protocolo os animais foram desafiados com cocaína (i.p) ou etanol (i.p), para a avaliação da sensibilização comportamental (P34-P35) (n=6) e da preferência condicionada por lugar (CPP) (P36-P45) (n=6). A quantificação por Western Blotting (n=6) das proteínas marcadoras de plasticidade, como os receptores dopaminérgicos D1R e D2R, c-Fos, FRA1 e Rac1, no estriado e no córtex pré-frontal (CPF) foi realizada imediatamente após o dia do teste da CPP no P45. Já para o segundo protocolo, os animais foram desafiados com cocaína (i.p) para a avaliação da sensibilização comportamental (P34-P35) (n=12), da CPP (n=10) e a quantificação dos mesmos marcadores bioquímicos (n=6) além da dinorfina-A, nas mesmas estruturas encefálicas que no primeiro protocolo. Essas análises foram realizadas duas horas após a expressão da sensibilização comportamental (P36). O primeiro protocolo avaliou a exposição repetida ao etanol e a cocaína na adolescência na predisposição à dependência enquanto o segundo se a exposição aguda a cocaína seria capaz de levar ao mesmo efeito. No primeiro protocolo observamos sensibilização cruzada pela PTA e quanto ao teste da CPP não foi observada diferença estatística nem para o tratamento com etanol, nem para o com cocaína. Nossos resultados indicam que houve efeito estimulatório nos grupos tratados com cocaína no segundo protocolo deste estudo, representado pelo aumento da atividade locomotora após administração da droga. Por outro lado, não observamos sensibilização cruzada pela PTA, a qual foi obtida no primeiro protocolo. Já para o segundo protocolo, foi observado o condicionamento pela cocaína. Com relação à quantificação das proteínas, nosso estudo mostrou diminuição na concentração de receptores DR1 no estriado no grupo exposto à PTA e tratado com etanol em relação ao grupo controle tratado com etanol no primeiro protocolo deste estudo e sugerem que a exposição repetida ao etanol é capaz de induzir alterações nos receptores de dopamina. No segundo protocolo deste estudo observamos aumento de c-Fos no estriado e no CPF no grupo tratado com cocaína em relação ao seu controle e que a exposição aguda à cocaína é capaz de induzir aumento da dinorfina no CPF, enquanto à exposição prévia à PTA previne este aumento. Vale ressaltar que esse trabalho é inovador uma vez que avaliamos a exposição à PTA na infância e se esta poderia levar a sensibilização cruzada com a cocaína e à alterações em vias envolvidas nesse comportamento na adolescência. Em conjunto, nossos resultados sugerem que a exposição à fumaça do cigarro, mesmo gerando baixas concentrações plasmáticas de nicotina e cotinina, foi capaz de produzir alterações na expressão da sensibilização comportamental, na CPP e alterações bioquímicas, tanto no tratamento repetido de etanol e cocaína quanto na vigência da cocaína. / The brain development represents a very vulnerable period. Although multiples studies showed that exposure to secondhand smoke during the early post-natal period induces impairment in cognitive functions and predisposition to substance dependence psychobehavioral symptoms in adolescents, there is no definitive evidences that exposure to the environmental tobacco smoke (ETS) can lead to the use of drugs of abuse. We aimed to evaluate if the exposure to ETS in the early postnatal period (P) can contribute to the behavioral sensitization and rewarding effects of ethanol and cocaine during adolescence. Using reference cigarettes (3R4F), Swiss-Webster male mice were exposed from the 3rd (P3) to 15th (P15) day of age, twice a day, to the mixture of the cigarettes\' sidestream and mainstream. In adolescence (P34-P45), we evaluated the effects of repeated treatment with ethanol or cocaine (first protocol) and also the effect of acute treatment with cocaine (second protocol). On first protocol, animals were then challenged with cocaine or ethanol to evaluate evidence of behavioral sensitization (P34-P35) (n=6) and conditioned place preference (CPP) (P36-P45) (n=6). Based on Western Blotting analysis, we also quantified proteins markers of plasticity immediately after the day of CPP test (P45), in the prefrontal cortex (PFC) and striatum (dopamine receptors D1R and D2R, c-Fos, FRA1 and Rac1). On second protocol, animals were challenged with cocaine to evaluate evidence of behavioral sensitization (P34-P35) (n=12) and CPP (P36-P45) (n=10). Quantification of those markers of plasticity (n=6), plus dynorphin-A was evaluated two hours after the day of behavioral sensitization expression in P36 in PFC and striatum. The first protocol evaluated the repeated exposure to ethanol and cocaine during adolescence in the predisposition to addiction while the second protocol using acute exposure to cocaine would be able to lead to the same effect. In the first protocol we observed cross-sensitization by ETS and for CPP test, no significant difference for the treatment with ethanol and cocaine were observed. Our results indicated a stimulatory effect in animals challenged with cocaine on second protocol, represented by the increase in locomotors activity after drug administration. On the other hand, we found no cross-sensitization by ETS, which was obtained in the first protocol. As for the second protocol, it was possible to observe the conditioning for cocaine. Regarding our Western Blotting assays, we observed that the group exposed to ETS and challenged with ethanol had decreased D1R in the first protocol of this study. These results suggest that repeated exposure to ethanol could induce changes in dopamine receptors. In the second protocol was an increase of c-Fos in the striatum and the PFC compared to control and that acute exposure to cocaine can induce increase of dynoprhin-A while the prior exposure to ETS prevents this increase on PFC. It is noteworthy that this present study is innovative since it evaluated the exposure to ETS in childhood and this could lead to cross-sensitization with cocaine and changes in pathways involved in this behavior in adolescence. Taken together, our results suggest that exposure to ETS, even findings low levels of nicotine and cotinine plasmatic was able to produce changes in the expression of behavioral sensitization in the CPP and biochemical changes in both the repeated treatment of ethanol and cocaine as in the acute treatment of cocaine.