La fonction publique française a mis en place depuis plusieurs années des initiatives de rémunération des agents publics en fonction de leurs performances. Le bilan mitigé de ces initiatives invite à questionner à la fois les effets recherchés (critères de performance) mais également les processus et les outils d’estimation de cette performance (politiques, évaluation, outils, etc.). Le constat le plus prégnant transparaît dans l’absence d’impact motivationnel des rémunérations basées sur la performance. Dans ce contexte, notre recherche vise à étendre le concept de rémunération au concept de rétribution globale orienté vers la performance, et incluant des éléments de rétributions extrinsèque et intrinsèque. Nous mobilisons le cadre d’analyse du contrat psychologique pour appréhender les effets de la rétribution globale sur les attitudes des agents territoriaux, en appréhendant les attentes implicites et les perceptions de réalisation du contrat psychologique dans le cadre de la dyade managers-collaborateurs. Nos principaux résultats confirment l’impact faible de la rémunération extrinsèque sur la performance individuelle des agents capturée par leurs attitudes. Ils montrent, a contrario, l’importance de la rémunération intrinsèque en termes de motivation, d’implication et de satisfaction. Ainsi, la rétribution extrinsèque et la rétribution intrinsèque doivent faire l’objet d’une stratégie globale, pensée par l’organisation et ses décideurs, autour d’un panachage approprié de rétribution extrinsèque et de rétribution intrinsèque en fonction des caractéristiques de l’organisation territoriale considérée. / The French public sector has implemented for several years some policies aiming to reward public employees regarding to their performance. The mixed results of these initiatives led to question the relevancy of the pursued objectives (performance criteria) as well as the relevancy of the process and of the tools used for evaluating employee performance (policies, evaluation, tools, and so on). One of the most important results is probably the absence of a motivational impact of a performance-based remuneration. In this regard, our research aims to extend the concept of performance-based remuneration to the concept of total reward, including extrinsic and intrinsic rewards. We select the “psychological contract” framework of analysis to understand the impact of a total reward, within French local organizations, on public employees’ attitudes. We especially collect employees’ implicit expectations and perceptions for understanding the realization of the “psychological contract” and its impacts on the dyad employee-manager. Our results confirm the limited impact of extrinsic rewards for enhancing employee performance, captured through their attitudes. They show, on the contrary, the importance of intrinsic rewards for employee attractiveness and loyalty. We conclude that extrinsic and intrinsic rewards should be carefully combined by managers within a global and planned rewarding strategy appropriate to each local organization’s characteristics.

A área tegmental ventral (VTA) contém neurônios dopaminérgicos do grupamento A10 e envia projeções muito densas para o estriado ventral. Esta circuitaria está crucialmente envolvida em mecanismos de recompensa. Recentemente, a organização destas projeções foi reexaminada por Ikemoto S. (Brain Res. Rev., 56:27-78, 2007), em um estudo de rastreamento retrógrado minucioso, sendo proposto a subdivisão destas projeções em um sistema dopaminérgico mesoestriatal ventromedial que inerva a concha medial do accumbens e o tubérculo olfatório medial, e um sistema dopaminérgico mesoestriatal ventrolateral que inerva o cerne e a concha lateral do accumbens e o tubéculo olfatório lateral. Afim de complementar o conhecimento destas projeções, no presente estudo elas foram examinadas com a técnica anterógrada da leucoaglutinina do Phaseolus vulgaris. Nossos resultados indicam que há um extenso embricamento dos campos terminais estriatais inervados por diferentes setores/núcleos da VTA e reforçam a noção de que as eferências da VTA podem ser subdivididas em um sistema mesoestriatal ventromedial e um sistema mesoestriatal ventrolateral. Eles revelam ainda que as projeções da VTA para o estriado ventral têm uma organização topográfica médio-lateral mais complexa do que previamente reconhecido, a faixa médio-lateral do estriado ventral inervada depende de uma combinação da região médio-lateral e dorsoventral da VTA. Assim, as regiões mais ventrais e mediais da VTA (correspondendo ao núcleo interfascicular) inervam os distritos mais mediais do estriado ventral (a concha dorsomedial do accumbens e a extremidade medial do tubérculo olfatório), e as regiões mais dorsais e laterais da VTA (correspondendo à região dorsolateral do núcleo parabraquial pigmentoso) se projetam para os distritos mais laterais do estriado ventral (o cerne lateral e a concha lateral do accumbens, o caudado-putâmen ventral e o tubérculo olfatório lateral). Por outro lado, as projeções da VTA para o estriado ventral não possuem uma organização topográfica rostrocaudal. Outro fato a ser destacado é que a organização das projeções mesoestriatais da VTA lembra o padrão das projeções córticoestriatais, sendo observado no estriado, além de um campo terminal principal, pequenos focos isolados de marcação. / The ventral tegmental area (VTA) contains dopaminergic neurons of the A10 group and sends dense projections to the ventral striatum. This circuitry is critically involved in reward mechanisms. Recently, the organization of these projections was reexamined by Ikemoto S. (Brain Res. Rev., 56:27-78, 2007) in a detailed retrograde tracing study, being proposed that these projections can be subdivided into two main systems, a ventromedial mesostriatal dopaminergic system that innervates the medial shell of the accumbens and medial olfactory tubercle, and a ventrolateral mesostriatal dopaminergic system that targets the core and lateral shell of the accumbens and lateral olfactory tubercle. In order to complement these data, in the present study the VTA mesostriatal projections were examined with a sensitive anterograde tracing technique using the Phaseolus vulgaris leucoaglutinin. Our results indicate that there is an extensive overlap of terminal fields innervated by different sectors / nuclei of the VTA and reinforce the notion that VTA efferents can be subdivided into a ventromedial and a ventrolateral mesostriatal system. They also show that the VTA projections to the ventral striatum have a mediolateral topographical organization more complex than previously acknowledged. In fact, projections along the mediolateral dimension of the ventral striatum depends on a combination of the mediolateral and dorsoventral axis of the VTA. In other words, the most ventral and medial parts of the VTA (corresponding to the interfascicular nucleus) innervates the most medial districts of the ventral striatum (corresponding to the dorsomedial shell of the accumbens and medial tip of the olfactory tubercle), and the most dorsal and lateral parts of the VTA (corresponding to the dorsolateral region of the parabrachial pigmented nucleus) project to the most lateral districts of the ventral striatum (lateral core and lateral shell of the accumbens, ventral caudate-putamen and lateral olfactory tubercle). Moreover, VTA projections to the ventral striatum do not seem to have a rostrocaudal topographical organization. It is also of note that the organization of the VTA mesostriatal projections shares features with cortico-striatal projections, in the sense that both fiber systems have a main terminal field and also give rise to small, scattered isolated foci of terminal labeling.

Cette thèse s’inscrit dans le cadre de la recherche sur les systèmes de dialogue. Ce document propose d’apprendre le comportement d’un système à partir d’un ensemble de dialogues annotés. Le système apprend un comportement optimal via l’apprentissage par renforcement. Nous montrons qu’il n’est pas nécessaire de définir une représentation de l’espace d’état ni une fonction de récompense. En effet, ces deux paramètres peuvent être appris à partir du corpus de dialogues annotés. Nous montrons qu’il est possible pour un développeur de systèmes de dialogue d’optimiser la gestion du dialogue en définissant seulement la logique du dialogue ainsi qu’un critère à maximiser (par exemple, la satisfaction utilisateur). La première étape de la méthodologie que nous proposons consiste à prendre en compte un certain nombre de paramètres de dialogue afin de construire une représentation de l’espace d’état permettant d’optimiser le critère spécifié par le développeur. Par exemple, si le critère choisi est la satisfaction utilisateur, il est alors important d’inclure dans la représentation des paramètres tels que la durée du dialogue et le score de confiance de la reconnaissance vocale. L’espace d’état est modélisé par une mémoire sparse distribuée. Notre modèle, Genetic Sparse Distributed Memory for Reinforcement Learning (GSDMRL), permet de prendre en compte de nombreux paramètres de dialogue et de sélectionner ceux qui sont importants pour l’apprentissage par évolution génétique. L’espace d’état résultant ainsi que le comportement appris par le système sont aisément interprétables. Dans un second temps, les dialogues annotés servent à apprendre une fonction de récompense qui apprend au système à optimiser le critère donné par le développeur. A cet effet, nous proposons deux algorithmes, reward shaping et distance minimisation. Ces deux méthodes interprètent le critère à optimiser comme étant la récompense globale pour chaque dialogue. Nous comparons ces deux fonctions sur un ensemble de dialogues simulés et nous montrons que l’apprentissage est plus rapide avec ces fonctions qu’en utilisant directement le critère comme récompense finale. Nous avons développé un système de dialogue dédié à la prise de rendez-vous et nous avons collecté un corpus de dialogues annotés avec ce système. Ce corpus permet d’illustrer la capacité de mise à l’échelle de la représentation de l’espace d’état GSDMRL et constitue un bon exemple de système industriel sur lequel la méthodologie que nous proposons pourrait être appliquée / This document proposes to learn the behaviour of the dialogue manager of a spoken dialogue system from a set of rated dialogues. This learning is performed through reinforcement learning. Our method does not require the definition of a representation of the state space nor a reward function. These two high-level parameters are learnt from the corpus of rated dialogues. It is shown that the spoken dialogue designer can optimise dialogue management by simply defining the dialogue logic and a criterion to maximise (e.g user satisfaction). The methodology suggested in this thesis first considers the dialogue parameters that are necessary to compute a representation of the state space relevant for the criterion to be maximized. For instance, if the chosen criterion is user satisfaction then it is important to account for parameters such as dialogue duration and the average speech recognition confidence score. The state space is represented as a sparse distributed memory. The Genetic Sparse Distributed Memory for Reinforcement Learning (GSDMRL) accommodates many dialogue parameters and selects the parameters which are the most important for learning through genetic evolution. The resulting state space and the policy learnt on it are easily interpretable by the system designer. Secondly, the rated dialogues are used to learn a reward function which teaches the system to optimise the criterion. Two algorithms, reward shaping and distance minimisation are proposed to learn the reward function. These two algorithms consider the criterion to be the return for the entire dialogue. These functions are discussed and compared on simulated dialogues and it is shown that the resulting functions enable faster learning than using the criterion directly as the final reward. A spoken dialogue system for appointment scheduling was designed during this thesis, based on previous systems, and a corpus of rated dialogues with this system were collected. This corpus illustrates the scaling capability of the state space representation and is a good example of an industrial spoken dialogue system upon which the methodology could be applied

Ce travail a interrogé les relations entre la victoire, la récompense et le vainqueur, dans les concours sportifs, en Grèce ancienne, du VIIIe s. av. J.-C. jusqu’à la prise de Corinthe par Mummius. Durant tous ces siècles, les concours, les récompenses et la place du vainqueur dans la cité ont connu des évolutions. Outre l’augmentation du nombre de rencontres et la constitution de la période, les récompenses ont aussi varié tant dans leur nature que dans leur signification. Nous avons étudié les rapports entre les trois termes de notre sujet selon trois perspectives : établir la victoire pour proclamer le vainqueur. Différents moyens sont alors lentement expérimentés, de la constitution d’un jury à l’équipement des lieux et à l’autopsis de la victoire, en passant par l’ouverture de nouvelles épreuves et catégories, tant humaines qu’animales. Puis comment la récompense et sa remise transforment l’athlète vainqueur sur le lieu même de son succès. A la cérémonie de proclamation et de couronnement dans le sanctuaire succèdent, dans un temps plus ou moins long, la mise en image et en mots. La victoire acquise et affirmée, la récompense reçue lui confèrent alors un statut nouveau et peuvent donner lieu à un enrichissement personnel. Dans une troisième partie nous avons analysé la relation entre l’athlète vainqueur et la cité de ses pères, selon trois axes : le premier met en évidence la rivalité entre certaines cités pour obtenir la gloire d’une proclamation. Le retour de l’athlète donne lieu à des cérémonies variées selon qu’elles sont familiales ou civiques. Enfin, nous avons confronté l’image négative transmise par certaines de nos sources à la carrière de quelques vainqueurs. / This PhD assessed the relations between victory, reward and victor in sport contests, both athletics and equestrianism, in Ancient Greece, from the 8.th century B.C. to the seizure of Corinth by Mummius. During all these centuries, increasing numbers of contests and rewards developed modifying the victor’s position in the city. By the way, cities organizing new contests, the « periodos » was established (the circuit of the Big Four Contests,) and the kind of rewards moved on the one hand to crowns and on the other to prizes. At the same time, the meaning of reward changed. We first examined the links between the three terms from three standpoints : first, reward and victor mean that victory in a contest is publicly set. Various means have been slowly tested to assert it, from building up the jury to sports facilities and victory autopsis, including new age groups or events, for humans as well as animals. Then we studied how reward and prize-giving change the athlete’s position on the spot of his victory. After he has been proclaimed and crowned in the sanctuary of the contests, the victor might publicly be praised or portrayed, even later on. Victory and reward gained give him a new position and could make him richer.

In the field of drug addiction, relapse back to drug seeking and taking is the major unmet clinical need. The rate of relapse back to drug-taking is ~70-80% within a year of drug abstinence. Gaining a better understanding of the prolonged neuronal changes that have taken place during drug addiction may lead to the design of better anti-relapse therapies. It is now widely believed that one component of drug addiction is by aberrant learning and memory processes. To study this, we investigated synaptic changes caused by the development of drug-seeking behaviour in C57BL/6J mice. Mice were treated either with non-contingent morphine or trained to exhibit drug-seeking behaviour following morphine-induced conditioned place preference (CPP) training, hippocampal slices were taken from these animals and synaptic changes examined at the CA3-CA1 synapse using electrophysiological methods. Mice that underwent morphine CPP were demonstrated to exhibit a significant preference for the morphine paired compartment before ex vivo electrophysiological analysis. Using field recordings, both non-contingent morphine and morphine CPP treatments resulted in a reduced ability to undergo stimulus-induced LTP compared to their respective controls. Whole cell patch clamp was then utilised to further investigate these effects. Non-contingent morphine treatment resulted in both pre- and post-synaptic changes with an increased AMPA:NMDA receptor ratio, concurrent increases in cell size, and reductions in the release probability of both glutamate and GABA. Morphine CPP treatment resulted in a more variable increase in AMPA:NMDA receptor ratio (presumably by the same mechanism but in a more specific group of neurones) and GABA release probability was also decreased. There were no detected increases in cell size however, or any detected changes in glutamate release probability. These findings therefore reveal a set of synaptic adaptations in the hippocampus unique to morphine-induced behavioural change, and may provide targets for future intervention in drug addiction.

Nosso grupo de pesquisa estuda ritmos circadianos em um roedor subterrâneo do gênero Ctenomys, o tuco-tuco. Nesta tese, apresentarei dados sobre sincronização fótica e não-fótica dos ritmos circadianos em tuco-tucos, e sobre sincronização não-fótica em camundongos. Investigamos a sincronização fótica em tuco-tucos por meio de uma abordagem conjunta de campo e laboratório. Inicialmente medimos o ciclo claro/escuro natural percebido por animais mantidos em áreas cercadas em campo, utilizando aparelhos light loggers que registraram continuamente o padrão temporal diário da exposição à luz. Em seguida, foi aplicado um modelo desse padrão de exposição à luz em laboratório, para testar o seu potencial como um sincronizador fótico dos ritmos circadianos dos tuco-tucos. O modelo consistiu em pulsos de luz aplicados uma vez por dia em diferentes momentos aleatórios. Apesar de carregar o mínimo de informação temporal, esse regime luminoso foi um sincronizador eficiente em muitos casos, tal como previsto anteriormente a partir de simulações computacionais de um oscilador matemático. Os resultados revelam que a sincronização de osciladores circadianos é ainda mais robusta do que se imaginava. Nosso segundo conjunto de experimentos avaliou a sincronização não-fótica em tuco-tucos, os quais são herbívoros, expostos a ciclos diários de disponibilidade de alimentos. Semelhante a outras espécies de roedores, tuco-tucos desenvolveram uma atividade antecipatória ao alimento, expressa diariamente antes da alimentação. Houve, no entanto, grande variabilidade inter-individual na expressão da atividade antecipatória, provavelmente relacionada com diferenças nas respostas metabólicas à restrição temporal do alimento. O trabalho final foi uma colaboração com o Dr. Shin Yamazaki, sobre sincronização não-fótica em camundongos do tipo selvagem e camundongos mutantes com ablação genética do relógio circadiano. Ciclos diários de alimentos palatáveis e de corrida em roda induziram ritmicidade autossustentada em camundongos mutantes arrítmicos, que não expressavam os genes Period, componentes importantes da maquinaria molecular que gera os ritmos circadianos nas células. Estes resultados sugerem a existência de novos osciladores circadianos que respondem a sinais diários de recompensa. Enquanto espécies modelo de laboratório, tais como o camundongo, podem trazer informações valiosas sobre os mecanismos fisiológicos, as espécies selvagens como o tuco-tuco podem nos dar pistas sobre o significado ecológico dos fenômenos circadianos / Our research group studies circadian rhythms in a subterranean rodent from the genus Ctenomys, the tuco-tuco. In this thesis, I will present data on photic and non-photic synchronization of circadian rhythms in tuco-tucos, as well as a study on non-photic synchronization in the laboratory mouse. Natural photic synchronization in tuco-tucos was verified with field and laboratory approaches. We initially measured the natural light/dark cycle experienced by tuco-tucos in semi natural field enclosures, by means of automatic light logger devices that continuously recorded the daily temporal pattern of light exposure. Next, a model of this light exposure pattern was applied to tuco-tucos in the laboratory, to test its potential as a photic synchronizer of the circadian rhythms. The model consisted of single light pulses applied once a day at varying random times. Despite the minimal timing information, this light regimen was a successful synchronizer in many instances, as predicted from previous computer simulations of a mathematical oscillator. These results revealed that the synchronization of circadian oscillators is even more robust than previously thought. Our second set of experiments evaluated the non-photic synchronization in the herbivorous tuco-tucos, by exposing animals to daily cycles of food availability. Similar to other rodent species, tuco-tucos in this protocol developed a circadian food anticipatory activity (FAA) right before the daily feeding time. However, there was great interindividual variability in FAA expression, likely related to differences in the metabolic responses to time-restricted feeding. The final work was a collaboration with Dr. Shin Yamazaki from the University of Texas Southwestern Medical Center, regarding non-photic synchronization in wildtype and mutant mice with genetic disruption of the circadian clock. Daily cycles of palatable food and wheel running induced self-sustaining rhythmicity in arrhythmic mutant mice, which do not express the Period genes, key components of the molecular machinery responsible for circadian rhythm generation within the cells. These results suggest the existence of novel circadian oscillators responsive to daily rewarding signals. While model laboratory species such as the mouse can bring valuable information on physiological mechanisms, wild species like the tuco-tuco can give us insights into the ecological meaning of circadian phenomena

The heterogeneity intrinsic to the ventromedial prefrontal cortex (vmPFC) is evidenced in both its anatomy and implicated function: vmPFC subregions have roles in positive affect, negative affect and autonomic/endocrine regulation. Whether different subregions serve fundamentally different functions, or whether they perform similar computations on different inputs, remains unclear. Nevertheless, the role of the vmPFC in psychopathology is widely appreciated - in mood and anxiety disorders, over-activity within constituent regions of the vmPFC is consistently implicated in symptomatology, together with its normalisation following successful treatment. However, the precise locus of change varies between studies. The work presented in this thesis investigates the causal contributions of over-activity within two key subregions of the vmPFC - the subgenual anterior cingulate cortex (sgACC, area 25) and perigenual anterior cingulate cortex (pgACC, area 32) - in discrete dimensions of behaviour and physiology affected in psychiatric disorders. Specifically, the impact of over-activity is assessed on (i) baseline physiological function; (ii) the regulation of anticipatory, motivational and consummatory aspects of reward-related behaviour; and (iii) negative affect including fear learning, stress recovery and the intolerance of uncertainty. To provide further insight into the mechanism of action of antidepressants, the efficacy of selected treatments is tested on changes induced by over-activity of these regions. Beyond the direct relevance of the results presented here to psychiatric disorders and their treatment, the thesis aims to emphasise the importance of broader themes associated with the measurement and quantification of emotion in preclinical animal studies. First, a multi-faceted approach is utilised enabling quantification of both the autonomic and behavioural aspects of emotion. In so doing, the experiments maintain relevance to studies which assess these correlates in isolation, both in humans (which typically measure subjective responses and physiology) and in rodents (which frequently assess behaviour in isolation). The assessment of more than one dimension of emotion confers these studies with improved power to detect maladaptive changes. Second, the experiments described were conducted in the marmoset, a new-world primate. The extensive anatomical homology between marmoset and human prefrontal cortex facilitates the forward-translation of functional results. In combination with the appropriate assays, this renders marmosets as an invaluable species to study the causal contributions of vmPFC subregions to symptoms of psychiatric disorders. I believe that the results of these experiments provide important insights into the causal role primate vmPFC has in relation to the behavioural and physiological aspects of psychiatric symptomatology. Most importantly, I hope that they serve as the foundation for future work to further elucidate the neuropathological processes underlying mental disorders.

Submitted by Filipe dos Santos (fsantos@pucsp.br) on 2017-04-27T12:40:16Z No. of bitstreams: 1 João Oswaldo Esotico.pdf: 1376718 bytes, checksum: 0132b952b251492c96e5304accc94de2 (MD5) / Made available in DSpace on 2017-04-27T12:40:16Z (GMT). No. of bitstreams: 1 João Oswaldo Esotico.pdf: 1376718 bytes, checksum: 0132b952b251492c96e5304accc94de2 (MD5) Previous issue date: 2017-04-20 / The objective of the present study was to examine how a strategic remuneration system, linked to a set of objectives, goals, indicators and initiatives that express the strategic uniqueness of an Organization and that can contribute to reach strategic implementations. For this verification, we conducted a case study with the retail trade company RaiaDrogasil, seeking to know if there is a relationship between its strategy - organic growth - and the systematic variable remuneration adopted at various levels of the organization. In order to verify this relationship, an analysis was made with the historical data of the company, in November / 2011, when the Raia and Drogasil drugstores were merged, both publicly traded, by 2015, comparing its physical expansion and increase of the company's value with the Shares traded on the stock exchange, as well as the various Remuneration models adopted for each area of the company, and levels of organizational command. The theoretical basis of the work is presented in two separate strands, one regarding the Strategy and its Implementation, and the other reasoning regarding the Strategic Remuneration, focused mainly on Variable Remuneration. It is verified that the study shows a relativity between the elaboration of the strategy and its implementation with participation of the variable remuneration in the achievement of the established goals / O objetivo do presente trabalho foi examinar como um sistema de remuneração estratégica, atrelado a um conjunto de objetivos, metas, indicadores e iniciativas que exprimam a singularidade estratégica de uma organização e que pode contribuir para atingir Implementações Estratégicas. Para esta verificação realizamos um estudo de caso com a empresa de comércio varejista RaiaDrogasil, buscando saber se há relação entre sua estratégia – Crescimento Orgânico – e a sistemática de remuneração variável adotada nos diversos níveis da Organização. Para verificarmos esta relação foi realizada uma análise com os dados históricos da empresa, no período de novembro/2011 data da fusão das drogarias Raia e Drogasil, ambas de capital aberto, até 2015, comparando sua expansão física e incremento do valor da empresa com as ações negociadas na bolsa de valores, bem como os diversos modelos de Remuneração adotados para cada área da empresa, e níveis de comando organizacional. A fundamentação teórica do trabalho é apresentada em duas vertentes separadas, uma quanto a Estratégia e sua Implementação, e a outra fundamentação no que tange à Remuneração Estratégica, focada principalmente em Remuneração Variável. Verifica-se que o estudo evidencia uma relatividade entre a elaboração da estratégia e sua implementação com participação da remuneração variável no desempenho de alcance das metas estabelecidas

Introdução: Evidências sugerem que alterações no ambiente intrauterino afetam o persistentemente o desenvolvimento de diferentes órgãos e sistemas de modo a programar o risco para doenças crônicas ao longo da vida. A restrição de crescimento intrauterino (RCIU) é associada com o aumento da preferência pelos alimentos palatáveis e risco para doenças metabólicas na vida adulta. Níveis alterados de insulina no ambiente fetal encontrados em indivíduos que sofreram RCIU podem modificar a formação das vias associadas ao prazer e recompensa (sistemas opioide e dopaminérgico), modificando o comportamento alimentar. O objetivo deste estudo foi avaliar possíveis alterações na resposta frente ao alimento palatável em animais submetidos à RCIU. Metodologia: No dia 10 de gestação ratas Sprague-Dawley receberam dieta à vontade (AdLib), ou dieta restrição de 50% (FR). No nascimento, houve adoção cruzada dos filhotes, gerando os grupos (gestação/lactação): AdLib/AdLib (Controles) e FR/AdLib (Restrição de Crescimento Fetal - FR). No estudo 1, foi avaliada a resposta hedônica dos animais em 2 momentos (nas primeiras 24h de vida e aos 90 dias de vida). Em ambas as idades os ratos receberam solução de sacarose ou água destilada e as respostas hedônicas faciais exibidas em 60 segundos foram analisadas. No estudo 2, na idade adulta (ratos machos ao redor dos 80 dias de vida) foi avaliado o consumo de dieta hiperpalatável e o nível de organização do comportamento alimentar usando o BioDAQ®, assim como a liberação de dopamina frente à ração padrão ou alimento palatável foi mensurada pela cronoamperometria no núcleo accumbens (NAcc), com ou sem o uso prévio de insulina sistêmica (5UI/kg) Resultados: Estudo 1; nos filhotes a resposta hedônica foi maior nos animais FR expostos a sacarose em comparação a água, sem diferenças nos filhotes do grupo controle. Houve diminuição na fosforilação do receptor mu opioide nos filhotes FR comparados aos controles. Na vida adulta, a resposta hedônica e a fosforilação mu opioide não foram diferentes entre os grupos, sugerindo que as alterações da resposta hedônica e a fosforilação mu opioide observadas no primeiro dia de vida não persistem. No estudo 2, existiu uma interação entre grupo e período do dia em relação ao consumo de ração hiperpalatável, os animais FR comeram mais ração hiperpalatável do que os controles no período ativo (ciclo escuro), e o padrão alimentar apresentou uma maior entropia (consumo imprevisível e fragmentado) no grupo FR neste ciclo. Existiu um atraso na liberação de dopamina no grupo FR em resposta ao Froot Loops® (tempo para a dopamina alcançar o pico máximo), mas não em resposta a ração padrão. O tratamento com insulina reverteu a diferença observada entre os grupos na resposta ao Froot Loops®. Western Blotting mostrou que SOCS3 diminui na área tegmentar ventral (VTA) dos FR; pTH/TH aumentou no NAcc de FR, como previamente demonstrado, mas similarmente aos achados da cronoamperometria, estas diferenças foram revertidas pela insulina Conclusão: Há alteração da resposta hedônica no primeiro dia de vida em animais RCIU, juntamente de modificações na fosforilação de receptores opioides, e estas diferenças não persistem na vida adulta. A RCIU altera a sensibilidade à insulina no VTA e consequentemente leva à modulação diferencial do sistema dopaminérgico, o que se reflete no padrão e preferência alimentar em machos adultos. A RCIU induz a alterações nos níveis de insulina possivelmente modificando a funcionalidade das vias hedônicas opioide e dopaminérgica. A RCIU programa alterações neurocomportamentais, afetando o comportamento alimentar, persistentes ao longo da vida que podem colaborar com o desenvolvimento da síndrome metabólica a longo prazo. / Introduction: Evidence suggests that alteration in the intrauterine environment persistently affects the development of different organs and systems and programs the risk for chronic diseases throughout the life. Intrauterine growth restriction (IUGR) is associated with increased preference for palatable foods and risk to metabolic disease in adulthood. Altered insulin levels in fetal environment in individuals who suffer IUGR can modify the development of the pathways associated with pleasure and reward (opioid and dopaminergic system), modifying eating behavior. The aim of this study was to evaluate possible changes in the brain response to palatable food in animals submitted to IUGR. Methods: At gestation day 10, Sprague-Dawley dams are assigned to receive ad libitum diet (AdLib) or 50% restricted diet (FR). At birth, pups were cross-fostered generating two groups (pregnancy/lactation): AdLib/AdLib (Controls) and FR/Adlib (Intrauterine growth restriction - FR). In the Study 1 the hedonic response of the animals was evaluated in 2 moments (24 hours after birth and at 90 days of life). In both ages, rats received sucrose solution or water and the hedonic facial responses exhibited within 60 sec were analyzed. The Study 2, in adulthood (male rats around 80 days of life) the palatable food consumption was evaluated and feeding behavior entropy was assessed using the BioDAQ®. The dopamine release facing standard chow and palatable food was measured by chronoamperometry recordings in nucleus accumbens (NAcc), with or without previous systemic insulin treatment (5UI/kg) Results: In the Study 1, pups’ hedonic responses were higher in FR pups exposed to sucrose as compared to water, without differences in Control pups. There was decreased phosphorylation of the mu opioid receptor in FR pups compared to Controls. In adult life, hedonic responses and mu opioid phosphorylation were not different between groups, suggesting that the alterations in hedonic response and in mu opioid phosphorylation observed in early life do not persist. In the Study 2, there was an interaction between group and time of the day on the palatable food consumption, FR rats eat more palatable foods than the Control group in the active period (dark cycle), and the eating pattern has a higher entropy (unpredictable and fragmented consumption) in the FR group in this cycle. There was a delayed dopamine release in the FR group in response to Froot Loops® (time to reach the peak dopamine release), but not in response to standard chow. Insulin treatment reverted the difference observed between groups in the dopamine (DA) response to Froot Loops®. Western blot showed that SOCS3 was decreased in the ventral tegmental area (VTA) of FR; pTH/TH was increased in the NAcc of FR, as we have previously shown, but similarly to the chronoamperometry findings, these differences was reverted by insulin Conclusion: There is an alteration in the hedonic response to sucrose in the first day of life in IUGR animals, together with modifications in opioid receptor phosphorylation, and these differences do not persist in adult life. IUGR alters insulin sensitivity in VTA and consequently leads to a differential dopaminergic modulation by insulin, which is reflected in the pattern and food preference in adult males. IUGR induces alterations in insulin levels possibly modifying the functionality of the opioid and dopaminergic hedonic pathways. IUGR programs neurobehavioral changes, affecting eating behavior, persistently throughout life that may contribute to the development of metabolic syndrome in the long term.

The ability to take effective decisions is fundamental for successful environmental adaptation and survival. In this thesis, I investigated situations in which decisions appear irrational, at least from certain standpoints. I conducted a behavioural decision-making experiment in two groups of macaques: controls and a group with ventromedial prefrontal cortex/medial orbitofrontal cortex (vmPFC/ mOFC) lesions. Some choices lead to compound outcomes composed of different constituent parts. Control macaques' decisions suggested their estimates of the value of the compound were biased away from the sum of the values of the constituents and towards their mean. Lesions of vmPFC/mOFC diminished the size of the effect so that macaques in some ways appeared to make more rational decisions. Based on the results of this experiment I devised a similar Functional Magnetic Resonance Imaging (fMRI) paradigm with the control animals. This demonstrated strong vmPFC/mOFC activity when similar decisions were made and suggested a value comparison process. In addition, I investigated the role of dopamine in learning using Fast-Scan Cyclic Voltammetry (FSCV), while rats performed a simple decision-making task. Theories about the role of dopamine in learning have focused on the possibility that it codes scalar reward value prediction errors. Less consideration has been given to the possibility that dopamine might reflect prediction errors about reward identities regardless of value. I measured dopamine in the nucleus accumbens when unexpected changes in reward value or identity occurred while rats executed a two-choice two-reward instrumental task. Dopamine levels in the nucleus accumbens reflected reward value prediction errors. In addition, however, they also reflected some information about reward identity under some circumstances. Further investigation suggested that this might be due to differences in the nutritional value of different reward types that did not have clear measurable impacts of behaviour in the tasks that I used.