Suchergebnisse

One aspect of the addictive process that has not been thoroughly investigated is the consequence of the frustrated state occurring when the drug is not available. The present study aimed to validate a novel operant model of frustrated expected reward in mice. C57BL/6J mice were trained in operant conditioning maintained by chocolate-flavoured pellets or cocaine. After the completion of high rates of responding on a progressive ratio schedule, the reward was unexpectedly withheld. The consequences of this frustrated behaviour on anxiety, aggressiveness, perseveration, extinction and reinstatement were investigated. Mice exposed to the frustrated event perseverated in the operant responses and showed increased aggressiveness in the resident-intruder test. These animals also showed higher rates of cue-induced reinstatement of drug seeking. The present study provides a reliable operant model in mice to evaluate a frustrated state following reward unavailability. This animal model could be useful to study the behavioural and neurochemical consequences related to the emotional states generated during the omission of a highly expected reward. ; This work was supported by the DG Research of the European Commission (PHECOMP, no. LHSM-CT-2007—037669 and GENADDICT, no. LSHM-CT-2004—05166), the Spanish 'Instituto de Salud Carlos III' (RTA, no. RD06/001/001), the Spanish 'Ministerio de Ciencia e Innovación' (no. SAF2007-64062), the Spanish 'Ministerio de Sanidad, Política Social e Igualdad' (Plan/nNacional Sobre Drogas, no. 2009/026), the Catalan Government (SGR2009-00131), the ICREA Foundation (ICREA Academia-2008). A.B. was supported by an FI pre-doctoral fellowship of the Catalan Government; J.G.-C. was supported by a 'Juan de la Cierva' postdoctoral fellowship from the Spanish 'Ministerio de Ciencia e Innovación'; and E.M.-G. was supported by a 'Sara Borrell' post-doctoral fellowship from the Spanish 'Instituto de Salud Carlos III'. Partial support from FEDER funds is also acknowledged

The pathophysiological mechanisms underlying depression are still poorly understood. An initial hypothesis postulated to explain the substrates of depression was based on the involvement of monoaminergic systems. This early theory was proposed from different findings obtained using pharmacological tools and can explain the mechanism of action of the drugs currently used to treat depression. However, more recent studies have revealed that other neurobiological processes different from monoamines also participate in the substrates of depression. These mechanisms include the participation of several neuromodulatory systems, stress-related circuits and neuroplastic changes that could represent a direct substrate for these pathophysiological processes. The lack of selective pharmacological tools for several of these potential targets of depression represents an important limitation to study their potential involvement. In the last two decades, different lines of genetically modified mice have been generated with selective deletions in specific genes related to the control of emotional responses. This review summarizes the main findings that have been obtained with these novel genetic tools to clarify the neurobiological substrates of depression. A particular focus has been devoted to the advances obtained with mice deficient in specific components of the monoaminergic, opioid and cannabinoid system and those with mutations in elements of the hypothalamic-pituitary-adrenal axis. ; This work was supported by the Spanish "Ministerio de Ciencia e Innovación" (#SAF2007-64062 and SAF2011-29864), "Instituto de Salud Carlos III" (RETICS-Red de Trastornos Adictivos-Redes Temáticas de Investigación Cooperativa en Salud: #RD06/0001/0001, #RD06/0001/1004), grants #10/00316 and #10/01708 to PR. Plan Nacional sobre Drogas (PNSD #2009/026), the Marató of TV3, the Catalan Government (SGR2009-00131) and the ICREA Foundation (ICREA Academia-2008)

Several lines of evidence support that food overconsumption may be related to the role of the endogenous opioid system in the control of food palatability. The opioid system, and particularly the delta opioid receptor (DOR), plays a crucial role in the regulation of food rewarding properties. In our study, we used operant conditioning maintained by chocolate-flavoured pellets to investigate the role of DOR in the motivation for palatable food and the structural plasticity changes promoted by this behaviour. For this purpose, we evaluated the specific role of this receptor in the behavioural and neuroplastic changes induced by palatable food in the prefrontal cortex (PFC), hippocampus (HCP) and nucleus accumbens (NAc) in constitutive knockout (KO) mice deficient in DOR. Mutant mice and their wild-type littermates were trained to obtain chocolate-flavoured pellets on fixed ratio 1 (FR1), FR5 and progressive ratio (PR) schedule of reinforcement. No significant differences between genotypes were revealed on operant behaviour acquisition in FR1. DOR knockout mice displayed lower number of active lever-presses than wild-type mice on FR5, and a similar decrease was revealed in DOR KO mice in the breaking point during the PR. This operant training to obtain palatable food increased dendritic spine density in the PFC, HCP and NAc shell of wild-type, but these plasticity changes were abolished in DOR KO mice. Our results support the hypothesis that DOR regulates the reinforcing effects and motivation for palatable food through neuroplastic changes in specific brain reward areas. ; This work was supported by the DG Research of the European Commission FP7 (#HEALTH-F2 2013-602891), the Spanish 'RETICS-Instituto de Salud Carlos III' (#RD12/0028/0023), the Spanish 'Ministerio de Ciencia e Innovación' (#SAF2011-29864), the Spanish 'Ministerio de Economia y Competitividad' (#SAF-2014-59648P), the 'Plan nacional sobre drogas' (#PNSD-2013-5068) and the Catalan Government 'AGAUR-Generalitat de Catalunya' (#2009SGR00731 and #2014-SGR-1547). The FEDER funds support is also acknowledged. S.M. was supported by FI predoctoral fellowship of the Catalan Government; S.M-N. was supported by CAPES fellowship of the Brazilian Government (Programa Ciência Sem Froteiras). We thank Elysia James for invaluable technical assistance in the structural plasticity study

BACKGROUND: Mu opioid receptors (MORs) are central to pain control, drug reward, and addictive behaviors, but underlying circuit mechanisms have been poorly explored by genetic approaches. Here we investigate the contribution of MORs expressed in gamma-aminobutyric acidergic forebrain neurons to major biological effects of opiates, and also challenge the canonical disinhibition model of opiate reward. METHODS: We used Dlx5/6-mediated recombination to create conditional Oprm1 mice in gamma-aminobutyric acidergic forebrain neurons. We characterized the genetic deletion by histology, electrophysiology, and microdialysis; probed neuronal activation by c-Fos immunohistochemistry and resting-state functional magnetic resonance imaging; and investigated main behavioral responses to opiates, including motivation to obtain heroin and palatable food. RESULTS: Mutant mice showed MOR transcript deletion mainly in the striatum. In the ventral tegmental area, local MOR activity was intact, and reduced activity was only observed at the level of striatonigral afferents. Heroin-induced neuronal activation was modified at both sites, and whole-brain functional networks were altered in live animals. Morphine analgesia was not altered, and neither was physical dependence to chronic morphine. In contrast, locomotor effects of heroin were abolished, and heroin-induced catalepsy was increased. Place preference to heroin was not modified, but remarkably, motivation to obtain heroin and palatable food was enhanced in operant self-administration procedures. CONCLUSIONS: Our study reveals dissociable MOR functions across mesocorticolimbic networks. Thus, beyond a well-established role in reward processing, operating at the level of local ventral tegmental area neurons, MORs also moderate motivation for appetitive stimuli within forebrain circuits that drive motivated behaviors. ; This work was supported by the Centre National de la Recherche Scientifique (BLK), Institut National de la Santé et de la Recherche Médicale (BK), Université de Strasbourg (BLK), Medical Research Council/Economic and Social Research Council interdisciplinary studentship (to HLK), the British Pharmacological Society (IK), the European Commission (Genaddict Grant No. LSHMCT2004-005166 to BLK), the U.S. National Institutes of Health (National Institute of Drug Addiction, Grant No. 05010 to BLK and National Institute on Alcohol Abuse and Alcoholism, Grant No. 16658 to BLK), the Canada Fund for Innovation, and the Canada Research Chairs (to BLK). Electrophysiological experiments were funded by the Intramural Programs of National Institute on Alcohol Abuse and Alcoholism and National Institute of Neurological Disorders and Stroke (Grant No. ZIA-AA000421 to VAA) and Japan Society for Promotion of Science (to AMats). Self-administration studies were supported by the Intramural Programs of National Institute on Alcohol Abuse and Alcoholism and National Institute of Neurological Disorders and Stroke (Grant No. ZIA-AA000421 to RM), the Directorate-General for Research of the European Commission Framework Programme 7 (Grant No. HEALTH-2013-602891 to RM), the Spanish Redes Temáticas de Investigación Cooperativa en Salud-Instituto de Salud Carlos III (Grant No. RD12/0028/0023 to RM), the Spanish Ministerio de Economia y Competitividad (Grant No. SAF-2014-59648P to RM), the Plan Nacional Sobre Drogas (Grant No. PNSD-2013-5068 to RM), and the Catalan Government Agència de Gestió d'Ajuts Universitaris i de Recerca (Grant No. 2014-SGR-1547 to RM) and Institució Catalana de Recerca i Estudis Avançats-Acadèmia (Grant No. 2015 to RM). Part of the work was supported by German Research Foundation Excellence Cluster EXC-1086 BrainLinks-BrainTools (to JH).

Partie 1. De la genèse de l'État malien : un long processus de sédimentation historique. - L'héritage précolonial dans la construction étatique malienne --. - La fabrique du Soudan. --. - Partie 2. Heurts et malheurs de l'institutionnalisation de l'état malien (1960-1992). - L'institutionnalisation manquée de l'État post-colonial --. - L'institution du politique et la production de l'État démocratique. --. - Partie 3. L'État malien en actes : les stratégies contrastées de son appropriation. - L'État modeste : bonne gouvernance et décentralisation --. - L'État au concret ou la construction continuée de l'institution --. - Le Mali 2012-2015 : de l'illusion à la désillusion

The article discusses the image of the German and Austro-Hungarian intervention in Ukraine in 1918 in Ukrainian memoirs. While these works generally describe the policies of the Central Powers toward Ukraine as imperialist and dictated by the military and economic interests of the two states, only the most radical leftist writers fail to appreciate the role German and Austrian troops played in the removal of Bolshevik forces from Ukraine. Common and individual portraits of the military and political apparatus of the intervention forces differ depending on the political position of the writer. Those who viewed the repressive policies toward rural Ukraine from the perspective of the elites of Kiev discuss them only in abstract terms. In general, Austro-Hungary's part in the intervention is described in less favourable terms than that of Germany. ; p. 37-64 ; The article discusses the image of the German and Austro-Hungarian intervention in Ukraine in 1918 in Ukrainian memoirs. While these works generally describe the policies of the Central Powers toward Ukraine as imperialist and dictated by the military and economic interests of the two states, only the most radical leftist writers fail to appreciate the role German and Austrian troops played in the removal of Bolshevik forces from Ukraine. Common and individual portraits of the military and political apparatus of the intervention forces differ depending on the political position of the writer. Those who viewed the repressive policies toward rural Ukraine from the perspective of the elites of Kiev discuss them only in abstract terms. In general, Austro-Hungary's part in the intervention is described in less favourable terms than that of Germany. ; s. 37-64

Equity is a central principle in Irish health policy and there is increasing political interest in altering the health financing structures in order to improve equity in the system. However, investigations of equity in Irish health care financing are out-dated and there are also concerns that available analytic measures are not adequately capturing patterns of inequity that are occurring in practice. The objectives of this thesis were to update and expand on previous analysis of equity in Irish health care financing by compiling more up-to-date data, developing and using alternative analytic methods, and identifying and modelling policy options for improving equity in the system. ; TARA (Trinity?s Access to Research Archive) has a robust takedown policy. Please contact us if you have any concerns: rssadmin@tcd.ie

Includes bibliographical references (p. 243-257) and index. ; Introduction: the politics of policy diffusion -- Enactment as a political process -- National activity and state political agendas -- National organizations and the information generation process -- Intrastate forces and the politics of customization -- Conclusion -- Appendix. ; Mode of access: Internet.

La liberalización del transporte aéreo que se llevó a término en la Unión Europea a principios de los años noventa ha tenido efectos positivos sobre el bienestar del viajero. No obstante, existe un consenso en la literatura académica que estos efectos dependen de la existencia de una competencia efectiva en el nivel de la ruta. En este sentido, se plantea el problema que puede llegar a suponer las ventajas de escalera de las compañías dominantes en cada mercado interior. Además, se pretende capturar la diferenciación de productos como característica esencial de la industria del transporte aéreo. El análisis de estas cuestiones se realiza de la forma siguiente. En primer lugar, se hace referencia a los principales aspectos económicos que condicionan la competencia en el transporte aéreo. Y en segundo lugar, se implementa un modelo empírico basado en un sistema de tres ecuaciones, que se estima mediante la técnica de las variables instrumentales. La muestra utilizada hace referencia al año 2001 para la mayoría de las rutas del mercado interior español de vuelos regulares en dónde hay competencia. Los resultados de la estimación muestran la existencia de unas condiciones de competencia diferentes según el segmento del mercado al cual se dirigen las compañías aéreas. Efectivamente, la competencia en precios (calidad) parece ser predominante en el segmento de viajeros por motivos personales (negocios). Adicionalmente, el dominio que la compañía dominante tiene sobre la mayoría de las rutas parece descansar en las ventajas competitivas, tanto en términos de costes como en términos de demanda, que le proporciona el control de la red aeroportuaria nacional. De todo esto se puede inferir que el mantenimiento y/o aumento de los beneficios de la liberalización de los servicios de transporte aéreo exige extender la liberalización al uso del aeropuertos así como descentralizar su gestión. ; - La liberalització del transport aeri que es va dur a terme a la Unió Europea a principis dels anys noranta ha tingut efectes positius sobre el benestar del viatger. No obstant, existeix un consens en la literatura acadèmica que aquests efectes depenen de la existència d'una competència efectiva en el nivell de la ruta. En aquest sentit, es planteja el problema que pot arribar a suposar ela avantatges d'escala de les companyies dominants en cada mercat interior. A més, es pretén capturar la diferenciació de productes com a característica essencial de la indústria del transport aeri. L'anàlisi d'aquestes qüestions es realitza de la forma següent. En primer lloc, es fa referència als principals aspectes econòmics que condicionen la competència en el transport aeri. I en segon lloc, s'implementa un model empíric basat en un sistema de tres equacions, que se estima mitjançant la tècnica de les variables instrumentals. La mostra utilitzada fa referència a l'any 2001 per a la majoria de les rutes del mercat interior espanyol de vols regulars en on hi ha competència. Els resultats de la estimació mostren l'existència d'unes condicions de competència diferents segons el segment del mercat al qual s'adrecen les companyies aèries. Efectivament, la competència en preus (qualitat) sembla ser predominant en el segment de viatgers per motius personals (negocis). Addicionalment, el domini que la companyia dominant té sobre la majoria de les rutes sembla descansar en els avantatges competitius, tant en termes de costos com en termes de demanda, que li proporciona el control de la xarxa aeroportuària nacional. De tot això es pot inferir que el manteniment i/o augment dels beneficis de la liberalització dels serveis de transport aeri exigeix estendre la liberalització a l'ús del aeroports així com descentralitzar la seva gestió ; The liberalisation of air transport that took place in the European Union at the beginning of the nineties has involved positive effects on the welfare traveller. However, there is an agreement in the academic literature that such effects depend on the existence of an effective competition at the level of the route. In this way, we deal with competition concerns referred to the scale advantages of major airlines in each domestic market. In addition to this, we try to capture product differentiation as one of the essential features of the airline industry. In order to achieve these goals, we firstly analyse the main economic aspects that determine competition in the airline industry. And secondly, we implement an empirical model based on a three equations system, which is estimated through the instrumental variables technique. The sample used includes most of routes of the Spanish domestic market of regular flights where competition does exist for 2001. Our results show the existence of different competition conditions according to the market segment in which airlines address their services. Indeed, price (quality) competition seems to be dominant in the segment of leisure (business) passengers. Furthermore, we also find that the major airline¿s dominance of the market relies on the competitive advantages in terms of cost and demand that provides the control of the Spanish airport network. We conclude that the maintenance and/or increase of the air liberalisation benefits require expanding liberalisation to airports space allocation and decentralising its management

Electronic Iran introduces the concept of the Iranian Internet, a framework that captures interlinked, transnational networks of virtual and offline spaces. Taking her cues from early Internet ethnographies that stress the importance of treating the Internet as both a site and product of cultural production, accounts in media studies that highlight the continuities between old and new media, and a range of works that have made critical interventions in the field of Iranian studies, Niki Akhavan traces key developments and confronts conventional wisdom about digital media in general, and contemporary Iranian culture and politics in particular. Akhavan focuses largely on the years between 1998 and 2012 to reveal a diverse and combative virtual landscape where both geographically and ideologically dispersed individuals and groups deployed Internet technologies to variously construct, defend, and challenge narratives of Iranian national identity, society, and politics. While it tempers celebratory claims that have dominated assessments of the Iranian Internet, Electronic Iran is ultimately optimistic in its outlook. As it exposes and assesses overlooked aspects of the Iranian Internet, the book sketches a more complete map of its dynamic landscape, and suggests that the transformative powers of digital media can only be developed and understood if attention is paid to both the specificities of new technologies as well as the local and transnational contexts in which they appear. This title was made Open Access by libraries from around the world through Knowledge Unlatched.--Provided by publisher. ; Includes bibliographical references and index. ; Acknowledgments -- Introduction: nascent networks -- Reembodied nationalisms -- Uncharted blogospheres -- The movable image -- Social media and the message -- Conclusion: new media futures -- Work cited -- Index. ; Electronic Iran introduces the concept of the Iranian Internet, a framework that captures interlinked, transnational networks of virtual and offline spaces. Taking her cues from early Internet ethnographies that stress the importance of treating the Internet as both a site and product of cultural production, accounts in media studies that highlight the continuities between old and new media, and a range of works that have made critical interventions in the field of Iranian studies, Niki Akhavan traces key developments and confronts conventional wisdom about digital media in general, and contemporary Iranian culture and politics in particular. Akhavan focuses largely on the years between 1998 and 2012 to reveal a diverse and combative virtual landscape where both geographically and ideologically dispersed individuals and groups deployed Internet technologies to variously construct, defend, and challenge narratives of Iranian national identity, society, and politics. While it tempers celebratory claims that have dominated assessments of the Iranian Internet, Electronic Iran is ultimately optimistic in its outlook. As it exposes and assesses overlooked aspects of the Iranian Internet, the book sketches a more complete map of its dynamic landscape, and suggests that the transformative powers of digital media can only be developed and understood if attention is paid to both the specificities of new technologies as well as the local and transnational contexts in which they appear. This title was made Open Access by libraries from around the world through Knowledge Unlatched.--Provided by publisher. ; Mode of access: Internet. ; Description based on print version record.