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Theses

Troubles anxio-dépressifs et antidépresseurs en préclinique chez le rat : évaluation de nouveaux traitements et de nouvelles modélisations comportementales

Abstract : Depression and chronic anxiety disorders are a major public health problem and conventional pharmacological strategies (antidepressants) appear often ineffective with a iatrogenic potential. In order to develop new treatments, animal models remain a solution of choice for evaluating the behavioral changes induced by these molecules. Creating new models more efficient seems to be a major field of investigation in order to optimize the role of filter of preclinical research. The objective of the work we present here is to propose some treatments exploiting new pharmacological tools like those with interaction with opioidergic pathways or with anti-oxidant properties. The results in the forced swimming test in rats show the antidepressant effects of a novel enkephalinase inhibitor, opiorphin, and of a cocoa polyphenolic extract. Secondarily, we present the development of new animal models in rats to better understand two types of clinical situations. We propose a new ethological model of extreme anxiety in which several reference treatments (chronic and acute fluoxetine, imipramine, diazepam and clonazepam) showed an efficacy comparable to that observed in panic disorder. On the other hand, a modeling procedure combining chronic mild stress to a chronic deficiency of methyl donors (folates in particular) leads to behavioral manifestations and neurobiochemical changes whose similarity with certain psychopathologies can be discussed (melancholic depression and panic disorder). The evaluation of new treatments and the development of new models set the foundations for promising research on anxiety-depressive disorders
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Theses
File URL :
http://docnum.univ-lorraine.fr/prive/DDOC_T_2012_0225_JAVELOT.pdf
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https://hal.univ-lorraine.fr/tel-01749623
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Submitted on : Thursday, March 29, 2018 - 12:21:30 PM
Last modification on : Tuesday, October 13, 2020 - 10:46:39 AM

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  • HAL Id : tel-01749623, version 1

Citation

Hervé Javelot. Troubles anxio-dépressifs et antidépresseurs en préclinique chez le rat : évaluation de nouveaux traitements et de nouvelles modélisations comportementales. Médecine humaine et pathologie. Université de Lorraine, 2012. Français. ⟨NNT : 2012LORR0225⟩. ⟨tel-01749623⟩

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