Efectos del estrés social sobre la memoria y su modulación farmacológica en ratones

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We have all experienced stress sometime in our lives, but what exactly is stress? This is a difficult question to answer because there are as many definitions of the term as people exist. Actually, Hans Selye, one of the founders of the modern concept of stress, stated that "everyone knows what stress is and at the same time no one knows what stress is" (Selye, 1973). More recently, McEwen and Wingfield (McEwen and Wingfield, 2003) stated that "the problem with the term stress is that it has too many meanings." The World Health Organization defines stress as "the set of physiological reactions that prepares the body for action" (WHO, 1994). These reactions are therefore necessary for adaptation to new situations that compromise survival of the organism by threatening its homeostasis. Thus, at first, stress would be adaptive since it helps the individual to behave adequately within its environment. However, when the stressful situation continues long time, we talk about chronic stress, emerging its maladaptative side. In fact, the great changes taking place in today's society, particularly in relation to new technologies, have turned stress into a public health problem of growing interest. In the case of humans, as a social species, the environment and the interpersonal relationships can be set as an inexhaustible source of stress. It is this type of social (or psychosocial) stress that increases the risk of a significant number of mental and physical disorders, becoming of particular relevance to carefully study its consequences. Thus, the main interest of this doctoral thesis is to evaluate the impact of chronic social defeat stress, a type of psychosocial stress in rodents, on cognition in mice, with emphasis on emotional memory, but also on spatial and recognition memory as well as the pharmacological modulation of these effects. The first chapter of this thesis contains a general introduction, beginning its first section with the biological and social definition of the term stress. The second section explains which animal models exist in social stress research, focusing on the intruder-resident model in rodents. Then, the third part defines what memory is, distinguishing between the main types of memory. The fourth section describes the different types of tasks for studying memory in animals, with special emphasis on emotional, spatial and recognition memory. Finally, the fifth and last section addresses the question of how stress affects memory, by briefly summarizing the main scientific findings in this regard. The second chapter is dedicated to the presentation of the main objectives and hypotheses of this doctoral thesis. The third chapter presents the first three studies, comparing the effects of chronic social defeat stress on emotional memory in postpubertal and adult mice. The fourth chapter presents studies 4 and 5, where the effects of different degrees of chronic stress of social defeat on emotional and spatial memory in postpubertal mice are studied. The fifth chapter presents study 6 focused on researching the effects of chronic social defeat stress on emotional memory in postpubertal mice and its modulation by the tricyclic antidepressant clomipramine. In the last study, the sixth chapter analyses the effects of chronic social defeat stress on emotional and recognition memory in postpubertal mice and its modulation by the anti-inflammatory indomethacin. The seventh chapter contains a general discussion where the main findings of the aforementioned studies, as well as the limitations and the future perspectives on this research topic are discussed. The eighth chapter collects the main conclusions of the studies included in this doctoral thesis. The ninth chapter includes a general summary of the Thesis presenting the objectives and hypotheses, the methodology and the studies carried out, the main findings, as well as the conclusions. The tenth chapter contains the references. Finally, the original articles are presented in a final section of annexes.
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