The role of differents subtypes of GABAergics interneurons on impulsive behavior and ethanol-seeking

• Grant number: 19/26246-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2020
• End date: April 30, 2023
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Fabio Cardoso Cruz
• Grantee: Fernando Bezerra Romualdo da Silva
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 18/15505-4 - Neurobiology study of relapse to alcohol and cocaine seeking: identification of plasticity in neuronal ensembles that encodes addiction-related memories, AP.JP2

Abstract

Ethanol is the most consumed drug of abuse in the world and plays an important role in public health problems, increasing morbidity and mortality rates, especially among adolescents. Studies show that the high prevalence of alcohol use at this stage of life may be related to impulsivity, loss of self-control and greater susceptibility to alcohol consumption. In this context, the insula or insular cortex seems to use an important role to control impulses, from its integrative action of interoceptive stimuli and executive functions, to evaluate a conflicting decision. In the insular cortex, the activation of different internal GABAergic subtypes modulates the activity of glutamatergic pyramidal neurons, the perception of danger ahead and immediate rewards. However, GABAergic interneurons are not homogeneous, including subtypes with multiple phenotypes, morphological and physiological profiles. Thus, it is necessary to investigate the role of these different subtypes of island action. Thus, the objective of the present project will be to investigate the role of different subtypes of cell GABAergic hormones without impulsive behavior and without ethanol-seeking behavior. Initially, animals can use behavioral testing (Elevated Zero-Maze Maze, Passive Avoidance, and Operant Conditioning) in 2 phases: adolescence and adulthood, to alter the test and the period most commonly used to perform impulsive tests. To identify the GABAergic interneurons associated, immunohistochemical techniques will be used. After defining the test and period, the relationship between the most impulsive and least impulsive animals and ethanol consumption (10%) will be evaluated through training in automatic administration boxes. Finally, after a behavioral evaluation (without period and more sensitive to impulsive behavior test), will be used the technique of chemogenetics, qualified by transgenic mice (SST-Cre and PV-Cre) and viral vectors that are used for selective evaluation. different subtypes of interneurons will attenuate or impulsive behavior as well as ethanol-seeking behavior. (AU)