Effects of Fluoxetine on Deficits in Aversive Memory Processes in the Contextual Fear Conditioning Model in Stressed Rats: Possible Involvement of 5HT-1A Receptors in the Medial Prefrontal Cortex

• Grant number: 24/02387-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): September 01, 2024
• Effective date (End): August 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Leonardo Resstel Barbosa Moraes
• Grantee: Ana Clara Magalhães Franzoni
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

In situations of danger, the organism triggers behavioral and physiological responses, including autonomic responses, to face the threat. Additionally, it is important to highlight that aversive memory is associated with these situations, playing a crucial role in the organism's survival. Memory formation involves distinct stages, including the processes of acquisition, consolidation (which can be short- or long-term), and retrieval. Specific brain regions play important roles in these memory processes. Individuals with Post-Traumatic Stress Disorder (PTSD), a neuropsychiatric disorder, exhibit deficits in the processes of forming and retrieving aversive memories.Animal models are essential for studying fear-associated responses and can be based on innate or learned fear. The Contextual Fear Conditioning (CFC) model is characterized by associating a neutral stimulus with an unconditioned aversive stimulus to create a conditioned response. The medial prefrontal cortex (mPFC) and the amygdala play a fundamental role in the formation, retrieval, and extinction of fear memory. Stress associated with this model causes alterations in the Hypothalamic-Pituitary-Adrenal (HPA) axis and affects monoamine neurotransmission, such as serotonin. Fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI), is used in the treatment of PTSD, improving the extinction of aversive memory and consequently reducing the recall of traumatic events.Given this, the project's hypothesis is that FLX will reverse the impairment in the extinction of contextual fear memory in stressed animals through the activation of 5HT-1A serotonergic receptors present in the mPFC.