Retrouvez toutes les discothèque Marseille et se retrouver dans les plus grandes soirées en discothèque à Marseille. Traffic Pro Die Klassiker-Reihe von Becker: Bereits seit 1999 gibt's die Traffic-Pro-Reihe (4720, 4723, 4725, 4733) - deren Navi-Lösungen viele Konkurrenten. Top VIdeos. Warning: Invalid argument supplied for foreach() in /srv/users/serverpilot/apps/jujaitaly/public/index.php on line 447. Update in the methodology of the chronic stress paradigm: internal control matters. Depression is projected to become the second most common cause of disability worldwide by 2. ![]() Depression as a major health issue is illustrated by its death- toll, which currently claims more lives per year than road- traffic accidents [1, 2, 3, 4]. At the same time, there is an obvious need for an improvement in the treatment of depression, as up to 4. The Diagnostic and Statistical Manual, Fourth Edition (DSM- IV) defines depression by the presence of at least one of two core symptoms: anhedonia; a decreased ability to experience pleasures, and depressive mood; lasting minimally 2 weeks [6, 7]. Since anhedonia, on the one hand, is a cardinal phenomenon of depressive disorders, and on the other, can be evoked in rodents, the hedonic deficit might be considered as a primary feature to be addressed in pre- clinical models of depression. Coping and cognitive deficits, low exploratory motivation, circadian and sleep disturbances, aggressive and anxiety traits, decreased sexual and increased submissive behaviour, social avoidance, deterioration of the coat state and other changes, which can be evoked in animals, with some considerations [8] are regarded as parallels of subsidiary depressive symptoms [9, 1. The aim of this review is to analyze the major methodological drawbacks in mouse models of depression with a focus on its principal feature, anhedonia, in a chronic stress paradigm, and to share with the reader several procedural modifications resulting from our own experiences with a chronic stress model in C5. \ USBclarifyFull.f with MD5.f and usb.ids included inline just for fun V1.0 Howerd Oakford www.inventio.co.uk \ Displays when a USB device is connected and. BL/6. N mice. We believe that the changes to methodology proposed here provide important advances in modelling the neurobiological basis of depression in rodents and that their implication can help develop more effective therapeutic strategies. Challenges in modelling depression and anhedonia using chronic stress paradigms. The chronic stress paradigm is considered to have a greater aetiological relevance and face validity in mimicking depression than other animal models, and therefore has become one of the most broadly used pre- clinical paradigms of this disorder [1. The first experiments using this model were undertaken by Katz and colleagues in rats, and involved rotating stressors applied over 2. These procedures were later modified by Willner resulting in higher length of experiment and lower severity of stressor [1. These experiments resulted in a decreased preference for, and intake of palatable solutions such as sucrose or saccharine. This was defined as stress- induced anhedonia. This anhedonic state was accompanied by an increase in the thresholds required for intracranial self- stimulation and was reversed by anti- depressants, but not by neuroleptics or anxiolytics [1. By now, a number of variants of chronic stress procedures had been proposed in both rats and mice and had been shown to evoke, in addition to anhedonia, the subsidiary depressive- like features mentioned above [1. Regrettably, a number of studies revealed inconsistencies in the induction of hedonic deficit in chronic stress models in both rats and mice [3. For example, in one study, Wistar and PVG hooded rats were subjected to chronic mild stress; stressed animals of both lines showed "unreliable" decreases in sucrose intake, which were "inconsistent" over time. None of stressed animals showed a decrease in the intracranial self- stimulation, evaluated by 5. Problems with reproducibility could also be due partly to the limited accuracy of the sucrose test, which, in its current state, does not have sufficient resolution to discriminate between anhedonic and non- anhedonic individuals within a stressed population [3. In addition, some of multi- disciplinary studies, using anhedonic chronic stress models of depression, have resulted in abstruse and contradictory outcomes, and failed to define a consistent molecular, neuroanatomical and physiological phenotype in either rats or mice. Data on their locomotion, anxiety, exploration, and other behaviours often demonstrated paradoxical and conflicting behavioural changes; many of them showed discrepancies between the behavioural phenotype of chronically stressed animals and human symptoms of depression. Together, controversies with reproducibility of stress- induced anhedonia, defined by sucrose preference data and identification of biological correlates of depression greatly limit the value of this method to model pre- clinical depression [4. Apart from methodological problems, application of the chronic stress approach has encountered some conceptual drawbacks. The most obvious is that in previously proposed models, all effects observed in groups of chronically stressed animals with signs of a decreased sensitivity to reward, are attributed to an hedonic deficit. It is important to note that stress alone can evoke a number of physiological alterations, which are not associated with a depressive- like behavior and anhedonia. With the originally proposed models and their analogues it was not possible to correlate findings obtained in chronically stressed animals with anhedonia, thus, specific biological correlates of hedonic deficit could not be addressed. Studies with our new model of stress- induced anhedonia suggest that unresolved methodological difficulties in measuring behaviour in chronically stressed animals may be the origin of the above problems. Here, we present data obtained across several experiments, which reveal the major sources of behavioural artifacts in chronic stress mouse models of depression. These data enable us to propose several changes to the accepted methodology which are validated by both behavioural and molecular correlates of anhedonia. Anhedonia is exhibited by a subgroup of animals in chronic stress paradigms. Numerous findings show a remarkable inter- individual variability in animals' responses to stress [9, 1. Using a principle of the isolation of responders and non- responders, we have established a mouse model of stress- induced anhedonia with an internal control for the effects of stress alone [4. A four week chronic stress paradigm, comprised of exposing male 3- months- old C5. BL6. N mice to tail suspension and restraint stress in different procedural variants resulted in a decrease of preference to 1% sucrose solution by ≤ 6. Figure 1]. It was shown that sucrose preference is similar in control, non- anhedonic and anhedonic mice before the onset of stress. At the end of the stress induction period sucrose preference and intake markedly decrease and are replaced by an increase in water consumption. Figure 1. Chronic stress results in decreased sucrose preference in a subgroup of mice. After initial increase in sucrose preference on the 3rd week of stress, by the termination of a 4- week stress, a cohort of mice display a prominent decrease in sucrose preference. Mice subjected to chronic stress were split into anhedonic and non- anhedonic subgroups according to the criterion of 6. Reproduction of this material is permitted by Macmillan Publishers Ltd. Recent studies in chronically stressed mice and rats have shown similar partial depressive- like outcomes ([2. Table 1). Resilience or susceptibility to stress- induced anhedonia and/or other physiological parallels of depressive- like state in newly developed models was found to correlate with distinct regulation of mesolimbic dopamine circuits, excitability of dopamine neurons of ventral tegmental area [2. Y, transcription and factors markers, immediate early genes, a dysfunction in the GABAergic system and AMPA- mediated transmission [2. Table 1. Partial depressive- like outcomes in chronic stress models of depression. The inter- individual variability in susceptibility or resilience to stress- induced decreases in sucrose preference observed in these, and our, paradigms suggest that this phenomenon is typical, even for inbred lines of animals [2. A variety of potential mechanisms may underlie this phenomenon: 1) pre- natal and early environmental factors [6. DNA and chromatin modifications, histone acetylation and methylation [6. DNA replicates [6.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. Archives
October 2017
Categories |