Restraint stress-induced long-lasting anxiety and contextual fear extinction impairment in rats: role of glucocorticoid and ghrelin receptors on BLA neuronal excitability

• Grant number: 15/15169-6
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): October 01, 2015
• Effective date (End): June 30, 2016
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Carolina Demarchi Munhoz
• Grantee: Leonardo Santana Novaes
• Supervisor: Ki Ann Goosens
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Research place: Massachusetts Institute of Technology (MIT), United States
• Associated to the scholarship: 12/24002-0 - Effects of environmental enrichment in long-lasting anxiety symptoms triggered by acute stress: implications in the emotional memory acquisition, BP.DR

Abstract

Anxiety-related disorders are common among psychiatric patients and are widely present in studies devoted to stress. In addition to the long-lasting anxiety behavior, impaired extinction of learned fear is associated with the development of post-traumatic stress disorder, one of the most debilitating anxiety-related disorder. Several approaches have been focusing on environmental influences on susceptibility and/or resistance of the organism to stress. Environmental enrichment (EE) is an experimental model that enhances the animal opportunity to interact with sensory, motor, and social stimuli compared to standard conditions. Among the benefits of EE are the improvement in learning and memory, as well as reduction in stress-induced behaviors, including anxiety. In a previous study, we found that exposure to EE prevented anxiety-related behavior in adult rats precipitated immediately after acute restraint stress. This protective role of EE on stress-induced anxiety seems to be due to the prevention of the stress-induced increase in neuronal activity and glucocorticoid receptor nuclear activity in the basolateral nucleus of the amygdala (BLA). Recently, we have shown that EE is also able to prevent the restraint stress-induced long-lasting anxiety and contextual fear extinction impairment in rats. Moreover, Dr. Goosens' lab has shown that chronic stress-related increases in circulating ghrelin are necessary and sufficient to stress-associated vulnerability in exacerbate fear learning, and that these actions occurred in the BLA. With that, the aim of this project is to generate viral vector constructs that will allow us to verify whether both long-lasting anxiety-like behavior and contextual fear extinction impairment triggered by acute stress are dependent on increased BLA neuronal excitability and/or GR nuclear activity. Finally, we will also determine whether the stress hormone ghrelin is elevated by acute stress, and examine the co-localization of the ghrelin receptor with GR activity (AU)