Avaliação do papel do córtex orbitofrontal, ínsula e córtex cingulado anterior na modulação da ansiedade induzida pelo modelo de transtorno de estresse pós-traumático em camundongos

• Main Author: Rosa, Luiz Augusto
• Publication Date: 2024
• Format: Doctoral thesis
• Language: por
• Source: Repositório Institucional da UFSCAR
• Download full: https://repositorio.ufscar.br/handle/20.500.14289/19987
• topic: Córtex cingulado anterior; Córtex orbitofrontal; Ínsula; Transtorno de estresse pós-traumático; Camundongos; Anterior cingulate cortex; Orbitofrontal cortex; Insula; Posttraumatic stress disorder; CIENCIAS HUMANAS::PSICOLOGIA

traumatic stress disorder (PTSD) is a psychiatric condition that results from exposure to severe traumatic events, with some of the main symptoms being: intrusive memories related to the trauma, constant avoidance, nightmares, hypervigilance and emotional helplessness. One of the main cognitive and behavioral processes related to PTSD is the difficulty in extinguishing the traumatic memory, which can persist for years or a lifetime. Among the various neural regions related to PTSD, we highlight the importance of the prefrontal cortex, responsible for both the coding and regulation of aversive responses, such as the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC) and the insula. To evaluate the role of these regions in modulating anxiety-type behaviors, we used male mice from the Swiss lineage that were subjected to a protocol for inducing PTSD based on a single exposure to foot shock (0.5 mA, 10s) in the dark side of the Dark-Light Box (DLB) followed by memory situations weekly in the light side of the DLB. To evaluate the modulation of aversive behavior, we performed injections of cobalt chloride (CoCl2), midazolam (GABAA-Benzodiazepine agonist, at doses 3.0 and 30.0 nmol) or saline intra-CCA, intra-COF and insula in animals that, then, they were exposed to the elevated plus maze (EPM), and subsequently re-exposed to DLB. Our data demonstrated that application of CoCl2 to both the CCA, OFC and insula significantly increased the number of entries and time spent in the open arms of the DLB, in addition to increasing the number of entries and time spent on the dark side of the DLB. In contrast, the application of intra-CCA midazolam did not show significant results in the DLB, only during re-exposure to the DLB, increasing the exploration of the dark side. As for the COF, although the application of MDZ increased the exploration of the open arms in the EPM, it decreased the exploration of the dark side of the CCE. In turn, application of MDZ to the insula increased both the exploration of the open arms of the DLB and the exploration of the dark side of the DLB in the reexposure test. The results demonstrated that the application of CoCl2 to the CCA, OFC and insula produced a significant increase in the percentages of the number of entries and time spent in the open arms of the CSF, in addition to increasing the number of entries and time spent on the dark side of the CSF. Intra-CCA midazolam did not change behaviors in the maze but increased LE exploration during re-exposure to CCE. Intra-COF midazolam injections increased the exploration of the open arms in the LCE but decreased the exploration of the LE of the CCE. However, intrainsula midazolam increased both the exploration of the open arms of the CSF and the exploration of the LE of the CCE in the reexposure test. Taken together, our results show that: i) inactivation of the CCA, COF and insula with cobalt chloride induced anxiolytic-like behavior in the CSF and CCE, suggesting that these three structures are areas that participate in the modulation of anxiety-like behavior in mice. ii) GABAergic neurotransmission from the OFC and the Insula participates in the emotional control associated with the aversive response investigated. However, the lack of effect on CCA suggests that other neurotransmissions, in addition to GABAergic, are involved in modulating these behaviors.