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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
351

Influência da manipulação neonatal sobre alterações metabólicas e neuroquímicas induzidas pela exposição crônica à dieta palatável na vida adulta

Benetti, Carla da Silva January 2010 (has links)
Estudos prévios demonstram que intervenções precoces levam a alterações comportamentais e neuroendócrinas na vida adulta. Nossos achados anteriores demonstram que animais manipulados no período neonatal consomem mais alimento palatável na vida adulta e apresentam um menor aumento do depósito de gordura abdominal, após exposição crônica a dieta palatável (chocolate) em relação aos animais intactos. Neste trabalho de tese, nosso objetivo foi avaliar os efeitos da manipulação neonatal sobre a preferência alimentar bem como sobre a regulação metabólica de ratas adultas. Para isso, investigamos parâmetros metabólicos e neuroquímicos em resposta à exposição crônica a uma dieta hipercalórica e palatável, assim como a um período de abstinência desse tipo de alimento em ratas fêmeas adultas expostas ou não à manipulação neonatal (10 min/dia, 10 primeiros dias de vida). A manipulação neonatal induziu maior ingestão de alimento palatável após um curto período de privação. Entretanto, o consumo durante a exposição crônica a essa dieta não diferiu entre os grupos experimentais. Também observamos que ratas fêmeas manipuladas, quando cronicamente expostas à dieta palatável na vida adulta, têm menor aumento da gordura abdominal e esse efeito persiste após a privação da dieta. Ratas não-manipuladas apresentaram níveis mais elevados de colinesterases no soro após exposição crônica a dieta palatável, entretanto, sem alterações na atividade de colinesterases no córtex cerebral. Foi identificado, após exposição crônica a dieta palatável, uma redução na atividade da enzima Na+,K+-ATPse no hipocampo e na amígdala e um aumento nos níveis plasmáticos de S100B em ratas não-manipuladas no período neonatal. Após as primeiras 24h de privação do alimento palatável, ratas fêmeas não-manipuladas demonstraram maior frequência de sinais de abstinência (tremores de cabeça) em comparação com ratas manipuladas no período neonatal. Assim, esses achados sugerem que a manipulação neonatal determina alterações persistentes no comportamento alimentar e previne algumas alterações periféricas e centrais induzidas pela exposição crônica a uma dieta hiperpalatável, modulando a resposta metabólica de modo a reduzir a vulnerabilidade de dano metabólico e neural. / Previous studies have demonstrated that an intervention early in life leads to behavior and neuroendocrine alterations in adulthood. According to our previous findings neonatallyhandled animals have an increased consumption of palatable food, as well as a lower increase in abdominal fat accumulation after being chronically exposed to a highly palatable diet (chocolate) as compared with intact rats. In the present study, our aim was to evaluate the effects of neonatal handling on food preference and metabolic regulation in adult female rats. Therefore, we investigated metabolic and neurochemical parameters in response to a chronic exposure to a highly palatable diet, and to its withdrawal in adult female rats exposed or not to neonatal handling procedure (10 min/day, 10 first days of life). We observed an effect of neonatal handling inducing an increased palatable food intake after one week of chocolate withdrawal. However, chocolate consumption during long-term exposure to this type of diet did not differ between experimental groups. After a 30-days-period of chocolate exposure, non-handled female rats exhibited an increased abdominal fat deposition in comparison to neonatally-handled rats, and this effect persisted even after chocolate withdrawal. Nonhandled rats had increased serum cholinesterase levels after chronic exposure to palatable diet, without alterations in cerebral cortex cholinesterase activity. We also observed that chocolate consumption lead to a reduced Na+,K+-ATPse activity in hippocampus and amygdala, as well as an increased plasma S100B levels in non-handled females rats. After the first 24h of chocolate withdrawal, non-handled female rats exhibited an increased frequency of head shakes, during the Open Field task, in comparison to handled rats. Therefore, these findings suggest that neonatal handling leads to persistent alterations in feeding behavior, and also prevents some peripheral and central alterations induced by chronic exposure to a highly palatable diet; modulating the metabolic response in order to reduce the vulnerability to metabolic and neuronal damage in adulthood.
352

Emily Dickinson in her private bubble : poems, letters and the condition of presence

Lied, Justina Inês Faccini January 2008 (has links)
The aim of this thesis is to show that Emily Dickinson was not concerned with the publication of her poems and she herself decided to withdraw from the outside world, a decisive event which contributed to the original production of her almost eighteen hundred poems and over eleven hundred letters. Emily Dickinson withdrew into her untouched private world – which here is called “the bubble” – and developed the contemplation process based on the approach of apprehending perceptions which resulted in the instant captions that have enchanted readers. Since her withdrawal was as a result of her own free choice and own writing and living conventions, she was able to be the craftsperson that enjoyed living and writing. Her perception of nature by taking instant captions of the observable natural objects is perfected by the process of contemplation developed in some of her poems. The theoretical and methodological basis of the study comes from the analysis of the complete edition of poems edited by Thomas H. Johnson, the letters edited by Mabel Loomis Todd, and the concept of Nature by Hans Georg Schenk. For the analyses of different issues related to Dickinson’s verses, withdrawal, and apprehension of perceptions, the works of the biographer Richard Benson Sewall and critics such as Albert Gelpi, Barton Levi Armand, Karl Keller, Sharon Cameron, among others, were consulted. This study aims to demonstrate that Emily Dickinson was not concerned with publication and her withdrawal within her bubble was a positive event for her life and poetry. Such conclusion might contribute to enlighten the knowledge about the life and work of such an amazing personage of American Literature and American society as Emily Dickinson has been so far.
353

Therapeutic techniques for treatment of adolescents with rebellious behaviour

Mathye, Lethabo Violet 25 August 2009 (has links)
This study focuses on the therapeutic interventions by mental health practitioners when faced with rebellious youths. Rebelliousness refers to the act of defying lawful authority or a resistant way of relating to authority or convention. It is manifested in, amongst others, withdrawal, deviance, delinquency, antisocial behaviour, and suicide. To date there are no interventions for rebellious youths per sé. Rebellious youths are often treated with traditional strategies which are often ineffective and show little promise for eliminating rebellious behaviour. Research has revealed that teen problem behaviours stem from "life-problems" such as psychosocial stressors. Therefore treating the adolescent for substance abuse, for example, is treating him/her for the wrong reasons. It is no surprise that many adolescents who have undergone intervention programmes for specific behaviour problems relapse soon after they are released from the programmes. The study focuses on integrating different strategies in order to combat rebelliousness in adolescence and beyond. This holistic approach argues that all treatments share certain curative processes. Therefore each treatment works best when it is combined with other aspects of treatment. For this reason, individual, family and group therapy were combined together with school strategies. The results of this study indicate that combining procedures that are designed to improve problematic behaviour in teenagers are viable forms of treatment. / Educational Studies / D.Ed.(Psychology of Education)
354

Semantic belief change

Meyer, Thomas Andreas 03 1900 (has links)
The ability to change one's beliefs in a rational manner is one of many facets of the abilities of an intelligent agent. Central to any investigation of belief change is the notion of an epistemic state. This dissertation is mainly concerned with three issues involving epistemic states: 1. How should an epistemic state be represented? 2. How does an agent use an epistemic state to perform belief change? 3. How does an agent arrive at a particular epistemic state? With regard to the first question, note that there are many different methods for constructing belief change operations. We argue that semantic constructions involving ordered pairs, each consisting of a set of beliefs and an ordering on the set of "possible worlds" (or equivalently, on the set of basic independent bits of information) are, in an important sense, more fundamental. Our answer to the second question provides indirect support for the use of semantic structures. We show how well-known belief change operations and related structures can be modelled semantically. Furthermore, we introduce new forms of belief change related operations and structures which are all defined, and motivated, in terms of such semantic representational formalisms. These include a framework for unifying belief revision and nonmonotonic reasoning, new versions of entrenchment orderings on beliefs, novel approaches to withdrawal operations, and an expanded view of iterated belief change. The third question is. one which has not received much attention in the belief change literature. We propose to extract extra-logical information from the formal representation of an agent's set of beliefs, which can then be used in the construction of epistemic state. his proposal is just a first approximation, although it seems to have the potential for developing into a full-fledged theory. / Computing / D.Phil.(Computer Science)
355

Influência da manipulação neonatal sobre alterações metabólicas e neuroquímicas induzidas pela exposição crônica à dieta palatável na vida adulta

Benetti, Carla da Silva January 2010 (has links)
Estudos prévios demonstram que intervenções precoces levam a alterações comportamentais e neuroendócrinas na vida adulta. Nossos achados anteriores demonstram que animais manipulados no período neonatal consomem mais alimento palatável na vida adulta e apresentam um menor aumento do depósito de gordura abdominal, após exposição crônica a dieta palatável (chocolate) em relação aos animais intactos. Neste trabalho de tese, nosso objetivo foi avaliar os efeitos da manipulação neonatal sobre a preferência alimentar bem como sobre a regulação metabólica de ratas adultas. Para isso, investigamos parâmetros metabólicos e neuroquímicos em resposta à exposição crônica a uma dieta hipercalórica e palatável, assim como a um período de abstinência desse tipo de alimento em ratas fêmeas adultas expostas ou não à manipulação neonatal (10 min/dia, 10 primeiros dias de vida). A manipulação neonatal induziu maior ingestão de alimento palatável após um curto período de privação. Entretanto, o consumo durante a exposição crônica a essa dieta não diferiu entre os grupos experimentais. Também observamos que ratas fêmeas manipuladas, quando cronicamente expostas à dieta palatável na vida adulta, têm menor aumento da gordura abdominal e esse efeito persiste após a privação da dieta. Ratas não-manipuladas apresentaram níveis mais elevados de colinesterases no soro após exposição crônica a dieta palatável, entretanto, sem alterações na atividade de colinesterases no córtex cerebral. Foi identificado, após exposição crônica a dieta palatável, uma redução na atividade da enzima Na+,K+-ATPse no hipocampo e na amígdala e um aumento nos níveis plasmáticos de S100B em ratas não-manipuladas no período neonatal. Após as primeiras 24h de privação do alimento palatável, ratas fêmeas não-manipuladas demonstraram maior frequência de sinais de abstinência (tremores de cabeça) em comparação com ratas manipuladas no período neonatal. Assim, esses achados sugerem que a manipulação neonatal determina alterações persistentes no comportamento alimentar e previne algumas alterações periféricas e centrais induzidas pela exposição crônica a uma dieta hiperpalatável, modulando a resposta metabólica de modo a reduzir a vulnerabilidade de dano metabólico e neural. / Previous studies have demonstrated that an intervention early in life leads to behavior and neuroendocrine alterations in adulthood. According to our previous findings neonatallyhandled animals have an increased consumption of palatable food, as well as a lower increase in abdominal fat accumulation after being chronically exposed to a highly palatable diet (chocolate) as compared with intact rats. In the present study, our aim was to evaluate the effects of neonatal handling on food preference and metabolic regulation in adult female rats. Therefore, we investigated metabolic and neurochemical parameters in response to a chronic exposure to a highly palatable diet, and to its withdrawal in adult female rats exposed or not to neonatal handling procedure (10 min/day, 10 first days of life). We observed an effect of neonatal handling inducing an increased palatable food intake after one week of chocolate withdrawal. However, chocolate consumption during long-term exposure to this type of diet did not differ between experimental groups. After a 30-days-period of chocolate exposure, non-handled female rats exhibited an increased abdominal fat deposition in comparison to neonatally-handled rats, and this effect persisted even after chocolate withdrawal. Nonhandled rats had increased serum cholinesterase levels after chronic exposure to palatable diet, without alterations in cerebral cortex cholinesterase activity. We also observed that chocolate consumption lead to a reduced Na+,K+-ATPse activity in hippocampus and amygdala, as well as an increased plasma S100B levels in non-handled females rats. After the first 24h of chocolate withdrawal, non-handled female rats exhibited an increased frequency of head shakes, during the Open Field task, in comparison to handled rats. Therefore, these findings suggest that neonatal handling leads to persistent alterations in feeding behavior, and also prevents some peripheral and central alterations induced by chronic exposure to a highly palatable diet; modulating the metabolic response in order to reduce the vulnerability to metabolic and neuronal damage in adulthood.
356

A desist?ncia de alunos na licenciatura em f?sica no Instituto Federal de Educa??o, Ci?ncia e Tecnologia do Rio Grande do Norte (IFRN): causas e sugest?es para o combate

Gomes, Fernando Costa Fernandes 05 August 2011 (has links)
Made available in DSpace on 2014-12-17T15:04:57Z (GMT). No. of bitstreams: 1 FernandoCFG_DISSERT.pdf: 4397896 bytes, checksum: 37f1c08102d90e6c9b8fe520fc84d920 (MD5) Previous issue date: 2011-08-05 / This dissertation proposes studying the issue of withdrawal undergraduate in physics at the Instituto Federal de Educa??o, Ci?ncia e Tecnologia do Rio Grande do Norte (IFRN) and collaborate with suggestions for dealing with this problem. The first chapter begins with an overview of two significant problems in the Brazilian educational system: the high dropout rates in degrees in physics and the lack of teachers with specific training in this science. Then, we discuss the relevance of this research to the area of physics teaching, as well as justify its completion as part of a professional master's degree. After, we present a proper definition for the term withdrawal, which is based on the existing problem in the IFRN. And, in the same chapter, we explicitly the focus, the objectives and the methodological aspects of this work. The results obtained in our investigation are presented in next four chapters. In the second chapter of this dissertation, we present: a brief history of the creation of IFRN degree in physics, the functioning of this course and the foundation of classrooms 2004.2 and 2006.1. We also show a kind of map of the withdrawal of the groups investigated (the dropout rate was 84.4% in both groups) and an analysis of the relationship between the curricula of each of them and the number of dropouts. In the third chapter, we display a descriptive statistics of the students which dropout and found that the largest dropout occurred with students who are women, married, parents of one kid; workers, joined with a minimum age of 23 years and completed high school at least 6 years. Then in the fourth chapter, we reveal and discuss the students' reports on the causes of their dropout. From the data presented, we can say that the answer to the question "What was the main reason for your dropout?" Is mainly in personal injury claims: another option for upper-level course and lack of time to devote to the course. In the fifth chapter, we show the results related to teacher s opinions about the phenomenon in question. We detected three main causes for the abandonment, according to teachers: the lack of dedication, the lack of interest and lack of integration in the course. In the sixth and final chapter, we discuss the results and present our conclusion and the proposed report - the product of this dissertation, presented as Annex. This report contains mainly suggestions for curricular and institutional actions that can contribute to reducing the dropout degree in Physics in the IFRN. The main actions suggested are: implementation of the curriculum in disciplines, implementation of programs or actions to combat this poor content of basic training, implementation of specific programs or actions for the student worker, and dissemination of IFRN degree in physics in schools through seminars or workshops / A presente disserta??o prop?e como quest?o-foco estudar a desist?ncia de licenciandos em F?sica no Instituto Federal de Educa??o, Ci?ncia e Tecnologia do Rio Grande do Norte (IFRN) e colaborar com a proposta de sugest?es para o enfrentamento dessa problem?tica. O primeiro cap?tulo se inicia com uma vis?o panor?mica de dois problemas significativos no sistema educacional brasileiro: as altas taxas de desist?ncia nas licenciaturas em F?sica e a falta de professores com forma??o espec?fica nesta ci?ncia. Em seguida, discutimos a relev?ncia desta pesquisa para a ?rea de ensino de F?sica, bem como justificamos a sua realiza??o no ?mbito de um mestrado profissionalizante. Apresentamos uma defini??o pr?pria para o termo desist?ncia, elaborado com base na problem?tica existente no IFRN. E, ainda no primeiro cap?tulo, explicitamos a quest?o-foco, os objetivos e os aspectos metodol?gicos deste trabalho. Os resultados obtidos em nossa investiga??o s?o apresentados nos quatro cap?tulos seguintes. No segundo cap?tulo desta disserta??o, apresentamos: um breve hist?rico da cria??o da licenciatura em F?sica do IFRN, o funcionamento deste curso e o surgimento das turmas 2004.2 e 2006.1. Tamb?m mostramos uma esp?cie de mapa da desist?ncia das turmas investigadas (o ?ndice de desist?ncia a 84,4% em ambas as turmas) e uma an?lise da rela??o entre os curr?culos de cada um delas e o n?mero de abandonos. No terceiro cap?tulo, exibimos uma estat?stica descritiva da caracteriza??o s?cio educacional do p?blico desistente e identificamos que as maiores desist?ncias ocorreram com alunos que s?o: mulheres; casados; pais de um filho; trabalhadores; ingressaram com idade m?nima de 23 anos e conclu?ram o ensino m?dio h? pelo menos 6 anos. Em seguida, no quarto cap?tulo, revelamos e discutimos os relatos dos alunos sobre as causas de suas desist?ncias. Diante dos dados apresentados, podemos afirmar que a resposta ? pergunta Qual foi o principal motivo da sua desist?ncia? encontra-se majoritariamente em causas pessoais: op??o por outro curso de n?vel superior e falta de tempo para se dedicar ao curso. No quinto cap?tulo, expomos os resultados relacionados ?s opini?es docentes sobre o fen?meno em quest?o. Detectamos tr?s principais causas para o abandono, segundo os professores: a falta de dedica??o; a falta de interesse; e a falta de integra??o no curso. No sexto e ?ltimo cap?tulo, discutimos os resultados obtidos e apresentamos nossa conclus?o e o relat?rio proposto produto desta disserta??o, apresentado como anexo. Esse relat?rio cont?m, principalmente, sugest?es de a??es institucionais e curriculares que podem contribuir para a redu??o da desist?ncia na licenciatura em F?sica no IFRN. As principais a??es sugeridas s?o: implanta??o da matriz curricular em disciplinas; implanta??o de programas ou a??es para combater a forma??o b?sica de conte?dos deficiente; implanta??o de programas ou a??es espec?ficos para o aluno trabalhador; e divulga??o da licenciatura em F?sica do IFRN em escolas por meio de semin?rios ou workshops
357

Consumer protection and State proposal in private self-regulation and administrative procedures: an initial approach / Protección al consumidor y propuesta Estatal en autorregulación privada y procedimientos administrativos: una aproximación inicial

Rejanovinschi Talledo, Moisés 12 April 2018 (has links)
Are State proposals on private self-regulation and administrative procedures on consumption adequate? The present papper analyzes the challenges of its application, providing a final reflection on the complaints in social networks. / ¿Son adecuadas las propuestas Estatales sobre autorregulación privada y procedimientos administrativos en materia de consumo? El presente artículo analiza los retos de su aplicación brindando una reflexión final acerca de los reclamos en redes sociales.
358

Influência da manipulação neonatal sobre alterações metabólicas e neuroquímicas induzidas pela exposição crônica à dieta palatável na vida adulta

Benetti, Carla da Silva January 2010 (has links)
Estudos prévios demonstram que intervenções precoces levam a alterações comportamentais e neuroendócrinas na vida adulta. Nossos achados anteriores demonstram que animais manipulados no período neonatal consomem mais alimento palatável na vida adulta e apresentam um menor aumento do depósito de gordura abdominal, após exposição crônica a dieta palatável (chocolate) em relação aos animais intactos. Neste trabalho de tese, nosso objetivo foi avaliar os efeitos da manipulação neonatal sobre a preferência alimentar bem como sobre a regulação metabólica de ratas adultas. Para isso, investigamos parâmetros metabólicos e neuroquímicos em resposta à exposição crônica a uma dieta hipercalórica e palatável, assim como a um período de abstinência desse tipo de alimento em ratas fêmeas adultas expostas ou não à manipulação neonatal (10 min/dia, 10 primeiros dias de vida). A manipulação neonatal induziu maior ingestão de alimento palatável após um curto período de privação. Entretanto, o consumo durante a exposição crônica a essa dieta não diferiu entre os grupos experimentais. Também observamos que ratas fêmeas manipuladas, quando cronicamente expostas à dieta palatável na vida adulta, têm menor aumento da gordura abdominal e esse efeito persiste após a privação da dieta. Ratas não-manipuladas apresentaram níveis mais elevados de colinesterases no soro após exposição crônica a dieta palatável, entretanto, sem alterações na atividade de colinesterases no córtex cerebral. Foi identificado, após exposição crônica a dieta palatável, uma redução na atividade da enzima Na+,K+-ATPse no hipocampo e na amígdala e um aumento nos níveis plasmáticos de S100B em ratas não-manipuladas no período neonatal. Após as primeiras 24h de privação do alimento palatável, ratas fêmeas não-manipuladas demonstraram maior frequência de sinais de abstinência (tremores de cabeça) em comparação com ratas manipuladas no período neonatal. Assim, esses achados sugerem que a manipulação neonatal determina alterações persistentes no comportamento alimentar e previne algumas alterações periféricas e centrais induzidas pela exposição crônica a uma dieta hiperpalatável, modulando a resposta metabólica de modo a reduzir a vulnerabilidade de dano metabólico e neural. / Previous studies have demonstrated that an intervention early in life leads to behavior and neuroendocrine alterations in adulthood. According to our previous findings neonatallyhandled animals have an increased consumption of palatable food, as well as a lower increase in abdominal fat accumulation after being chronically exposed to a highly palatable diet (chocolate) as compared with intact rats. In the present study, our aim was to evaluate the effects of neonatal handling on food preference and metabolic regulation in adult female rats. Therefore, we investigated metabolic and neurochemical parameters in response to a chronic exposure to a highly palatable diet, and to its withdrawal in adult female rats exposed or not to neonatal handling procedure (10 min/day, 10 first days of life). We observed an effect of neonatal handling inducing an increased palatable food intake after one week of chocolate withdrawal. However, chocolate consumption during long-term exposure to this type of diet did not differ between experimental groups. After a 30-days-period of chocolate exposure, non-handled female rats exhibited an increased abdominal fat deposition in comparison to neonatally-handled rats, and this effect persisted even after chocolate withdrawal. Nonhandled rats had increased serum cholinesterase levels after chronic exposure to palatable diet, without alterations in cerebral cortex cholinesterase activity. We also observed that chocolate consumption lead to a reduced Na+,K+-ATPse activity in hippocampus and amygdala, as well as an increased plasma S100B levels in non-handled females rats. After the first 24h of chocolate withdrawal, non-handled female rats exhibited an increased frequency of head shakes, during the Open Field task, in comparison to handled rats. Therefore, these findings suggest that neonatal handling leads to persistent alterations in feeding behavior, and also prevents some peripheral and central alterations induced by chronic exposure to a highly palatable diet; modulating the metabolic response in order to reduce the vulnerability to metabolic and neuronal damage in adulthood.
359

Právní následky porušení smlouvy v občanském právu / Legal consequences of a breach of contract in civil law

Antošová, Eliška January 2015 (has links)
The topic of this Master's degree thesis is "Legal consequences of breach of contract in civil law". The aim of this thesis is especially to analyse the legal consequences of the breach of contract under civil law. The text is divided into six chapters. Each chapter characterizes the particular consequence of the breach of contract. Each chapter also shows main differences and and possible advantages or disadvantages its enactment in the new Civil Code that came into effect on 1st January 2014. The first chapter deals with the pre-contractual liability. This chapter includes description of the pre- contractual negotiation and its main elements recognized within the framework of the Czech legal system. The chapter two analyzes aspects of delay in civil commitments in the law system of the Czech Republic with focus on the consequences a delay may cause. The third chapter explains essential points of the withdrawal from a contract. The fourth chapter describes and analyzes the legal institute of liability for defects, the issues regarding the liability for defect, its impact and also mentions some practical aspects related to it.Chapter five deals with the civil liability for damage. The aim of this chapter is to provide a basic overviewand to clarify crucial aspects of this legal institute. Chapter six...
360

Dépendance aux drogues opiacées : focus sur le système corticotropin-releasing factor / Opiate dependence : focus on the corticotropin-releasing factor system

Rouibi, Khalil Adnane 21 December 2011 (has links)
La prise illicite de drogues opiacées est un problème majeur de santé publique dans le monde. L’apparition du syndrome de sevrage aux opiacés (SAO) suite à l’arrêt de prise d’opiacés est considérée comme élément clef dans la vulnérabilité associée à la rechute de prise d’opiacés. En effet le syndrome de SAO est caractérisé par des altérations comportementales et neurobiologiques en réponse au stress qui sont déterminantes dans le phénomène de dépendance aux opiacés. Le système corticotropin-releasing factor (CRF) est un coordinateur central des circuits de réponse au stress par l’intermédiaire de ses deux récepteurs le: CRF1 et CRF2. L’objectif de cette thèse est de déterminer le rôle du récepteur CRF2 dans l’apparition des états affectifs négatifs et des désordres motivationnels impliqués dans la rechute de la consommation de drogues opioïdes lors du SAO.Nous avons démontré par une série d’expériences conduite chez des souris invalidées au récepteur CRF2 (CRF2-/-), que la délétion génétique du récepteur CRF2-/- éliminait les états dysphoriques ainsi que les altérations moléculaires induites par le SAO sans détériorer les réponses neuroendocriniennes qui sont primordiales lors des adaptations aux stress associées au sevrage. De surcroît, nous avons trouvé que les souris CRF2-/- entrainées dans une procédure de tâche opérante dirigée vers l’obtention d’une nourriture palatable, montraient une diminution des troubles motivationnels induits par le SAO. Plusieurs rapports montrent que chez l’Homme, les évènements stressants apparaissant lors d’une période de sevrage provoquent une rechute de la consommation d’alcool ou de drogues. Nous avons développé un modèle murin qui montrait un rétablissement de recherche de nourriture palatable suite à une procédure de stress appliquée pendant une période de SAO. Par ailleurs, nous avons observé un dimorphisme sexuel du rôle du récepteur CRF2 dans le rétablissement de recherche de nourriture palatable, suite au stress, longtemps après un SAO.Les résultats de ce travail de thèse nous permettent de mettre en avant le récepteur CRF2 comme possible cible thérapeutique dans le traitement de la dépendance aux opiacés. / Opiate illicit use represents one of the most severe sanitary problems throughout the world. Among humans, the emergence of the opiate withdrawal (OW) syndrome after cessation of opiate intake is considered as one of the key motivational elements that lead to the vulnerability to opiates relapse. Therefore, the OW is characterized by a various alterations of the behavioral and neurobiological homeostasis responses to stress which are determinants in opiate dependence. The Corticotropin-releasing factor (CRF) system is the major coordinator of stress-responsive circuitry. Through its two receptors CRF1 and CRF2, the CRF system has recently emerged as major contributor in the development of components of the OW syndrome. The aim of this thesis is to determine the role of CRF2 receptor in the negative affective states and motivational disorders implicated in opiate relapse during OW.Behavioral and biological experiments were conducted in CRF2 receptor-deficient mice (CRF2-/-). We reported that genetic deletion of the CRF2 receptor eliminates dysphoria and molecular alterations elicited by OW without impairing brain, neuroendocrine and autonomic stress-coping responses to withdrawal. Using behavioral approaches of operant responding to highly palatable food (HPF) we found that CRF2-/- reduces motivational disorders induced by intermittent morphine injections and withdrawal. Finally, we described a mouse model of stress-induced food reinstatement seeking behavior during prolonged OW. Furthermore, we reported a gender dimorphism in the role of the CRF2 receptor in the stress-induced reinstatement of HPF seeking behavior long-lasing after opiate treatment.These findings underscore the importance of CRF2 receptor as possible effective treatment of the critical problem of opiate dependence.

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