Navegando por Palavras-chave "Trauma-Related Disorders and Stress Factors"

Agora exibindo 1 - 1 de 1
  • Imagem de Miniatura
    Item
    Acesso aberto (Open Access)
    Variabilidade individual das respostas comportamentais e neurobiológicas em um modelo de estresse traumático baseado no condicionamento de medo ao contexto
    (Universidade Federal de São Paulo (UNIFESP), 2019-05-30) Careaga, Mariella Bodemeier Loayza [UNIFESP]; Suchecki, Deborah [UNIFESP]; Girardi, Carlos Eduardo Neves [UNIFESP]; http://lattes.cnpq.br/0014777128958249; http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4781617Z1; http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4417799A2; Universidade Federal de São Paulo (UNIFESP)
    Background: The exposure to highly stressful situations may induce behavioral and neurobiological modifications characteristics of post-traumatic stress disorder (PTSD), a condition defined by the recollection of the trauma, avoidance of traumarelated cues and increased arousal. Since not all trauma-exposed individuals develop PTSD, individual variability in response to stress is an important aspect that should be more addressed by animal models of PTSD, increasing the translational value of these models and allowing the investigation of vulnerability and resilience factors. Persistence of traumatic memories is a relevant aspect of PTSD and, therefore, investigation of the mechanisms supporting maintenance of traumatic memories may broaden the understanding of the neurobiological changes essential to this process, as well as allow the evaluation of treatments that could mitigate the psychological and/or phisyological alterations related to these memories. Objectives: To investigate the behavioral and neurobiological modfications in different subsets of animals submitted to a traumatic stress based on contextual fear conditioning and to assess whether a pharmacological internvention of the traumatic memory would mitigate other behavioral changes observed in highly reactive rats. Methods: Male adult Wistar rats were submitted to the traumatic stress (shock context group) and then classified into low, intermediary and high reactive animals, using the freezing time during the first re-exposure to the shock-paired context. All groups were then exposed to the elevated plus maze to assess anxiety-like and exploratory behaviors, to the non-associative fear test to assess inate fear response, and to an additional re-exposure to the shock-paired context. In Experiment I the effect of a previous habituation procedure on the outcomes of the traumatic stress was evaluated. Rats were habituated (shock context habituated) or not (shock context non-habituated) to experimental procedures prior the traumatic stress. In Experiment II, we assessed the behavioral and neurobiological modifications on different subgroups of stress-exposed animals. Fos expression was evaluated in several brain regions and used as a marker for neuronal activity. In Experiment III, we assessed whether the disruption of traumatic memory reconsolidation, by the administration of the β-adrenergic antagonist propranolol, would mitigate the behavioral alterations observed on high reactive rats. Results: In Experiment I, no differences in the expression of fear responses were found between the habituated and non-habituated shock context groups during the associative and non-associative tests. The habituation prior to the traumatic stress attenuated some behavioral alterations observed in the elevated plus maze. In Experiment II, the individual variability analysis allowed us to identify a more reactive subgroup of rats. These animals expressed greater associative and non-associative fear responses, anxietylike behavior and impaired exploration in the elevated plus maze. Correlation analyses in the more reactive group suggested an opposite activity pattern between the medial prefrontal cortex (mPFC) and the ventral hippocampus (vHPC) after the first re-exposure to the shock-paired context. Positive correlations were found between post-tone freezing and Fos expression in the dorsomedial periaqueductal gray (dmPAG), the ventral/dorsal hippocampus (v/dHPC) and the mPFC. In Experiment III, propranolol treatment after traumatic memory reactivation did not disrupt the expression of the associative fear response in high reactive animals, but, when administered 15 days after traumatic stress, it atenuated the fear response of these animals when confronted with an unknown stimulus. Conclusions: The habituation procedure prior to the traumatic stress did not greatly impact the behavioral profile. The individual variability analysis allowed us to identify different subsets of rats in the shock-context rat population. More reactive animals showed behavioral modifications that resembled symptoms observed in PTSD patients. The positive correlations between post-tone freezing and Fos expression in the dmPAG and vHPC suggested that these structures may play a role in the expression of fear response to unrelated trauma stimuli. The effect of propranolol given 15 days after the traumatic stress on non-associative fear suggested an effect of the intervention on fear sensitization process.