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Henes, Kathrin (2012): Traces of a trauma - pharmacological interventions of PTSD. Dissertation, LMU München: Faculty of Biology
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Abstract

Posttraumatic stress disorder (PTSD) is characterized by exaggerated trauma-related memories (contextual fear), increased avoidance of trauma-related cues, and hyperarousal. Pharmacotherapy of PTSD is still unsatisfactory, with SSRIs being the first choice drugs. However, as known for depressed patients, PTSD patients are prone for relapse of symptoms upon discontinuation of treatment. This urges for a refinement of therapeutic interventions and the identification of markers of treatment success. These issues were addressed in our mouse model of PTSD. In this model, mice are exposed to a brief, inescapable electric foot shock. Within 1 month after the trauma, they developed PTSD-like symptoms such as generalized contextual fear, generalized avoidance, and increased hyperarousal symptomatology. This time frame allows for pharmacological interventions during maturation of PTSD-like symptoms (i.e. preventive treatment) or at time points when the symptoms have fully developed (i.e. therapeutic treatment). The work presented in this thesis revealed the following key findings: (1) Fear incubation (i.e. simply the passage of time after trauma) was accompanied by highly selective changes in neuronal activity, as assessed by cytochrome c oxidase (CO) activity >1 month after trauma. (2) Chronic treatment with fluoxetine via drinking water starting either right after the trauma (preventive treatment) or 28 days later (therapeutic treatment) completely reversed the PTSD-like symptoms assessed during ongoing treatment 1 (preventive treatment) or 2 months (therapeutic treatment) after trauma. (3) Despite the similarities to PTSD-like symptoms, preventive treatment with fluoxetine abolished most of the trauma-related changes in CO activity, whereas those changes were maintained after therapeutic intervention. (4) If fluoxetine was washed out after 1 month of treatment, PTSD-like symptoms remained absent following preventive treatment, but re-occurred after therapeutic treatment. In conclusion, these data suggest preventive treatment with fluoxetine starting in the early aftermath of a trauma as a successful intervention strategy for preventing the development of PTSD-like symptoms. In contrast, therapeutic treatment abolishes the expression of symptoms, without curative effects. Chronic changes in CO activity reflect traces of a trauma. They might serve as an indicator of PTSD relapse.