Evaluation of the role of the pre-frontal cortex, Ínsula, and anterior cingulate cortex in the modulation of anxiety induced by the post-traumatic stress disorder model in mice

• Grant number: 17/27025-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): November 01, 2018
• Effective date (End): February 28, 2022
• Field of knowledge: Humanities - Psychology - Physiological Psychology
• Principal Investigator: Azair Liane Matos Do Canto de Souza
• Grantee: Luiz Augusto Rosa
• Host Institution: Centro de Educação e Ciências Humanas (CECH). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

Numerous studies have shown that states of anxiety, despite being positively correlated with hyperactivation of the amygdala and insula, have been correlated with generalized hypoactivity in the prefrontal cortex (negative correlation), which has been called hypofrontality in states of anxiety. Some studies have shown that patients with Posttraumatic Stress Disorder (PTSD) present generalized prefrontal hypoactivity, especially in the ventromedial prefrontal cortex, rostral CCA and medial frontal gyrus, both in tasks related to trauma and in tasks not related to trauma. Since there is still no consensus in the literature about why and how this occurs, our goal here will be to investigate the involvement of the Prefrontal Cortex (PFC) and insula in the modulation of anxiety induced in mice by the PTSD model. To do so, we will use male mice of the Swiss strain that will be submitted to the protocol for induction of PTSD, as follows: different groups of mice will undergo aversive conditioning with shock on the paws in the light-dark box on the 1st day of the experiment with recall situations in the 7th, 14th and 21 days of the experiment, where the mice will be reexposed to the light side of the light-dark box. For Experiments 1, 2 and 3, at day 28, the animals will be exposed to the elevated plus maze after application of CoCl2 or saline in the insula, CPF or Anterior Cingulate Cortex (ACC), and at day 34, they will be reexposed to the light-dark box after application of the same substances. In experiments 4, 5 and 6, at day 28, animals will be exposed to the elevated plus maze after application of midazolam or saline in the structures described above. At day 34, after application of midazolam, as described above, they will be reexposed to the light-dark box. In experiment 7, from the same experimental protocol, but without drug administration, we will measure and evaluate the expression of c-Fos in the PFC, ACC and insula of the animals. Thus, we will seek to deepen our understanding of the participation of these central nervous system structures in the modulation of behavioral anxiety responses associated with PTSD. (AU)