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Alcohol and the gut-brain axis: investigating post ingestive and gustatory effects on the striatum

Grant number: 19/13128-1
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): February 01, 2020
Effective date (End): January 31, 2021
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal Investigator:Fabio Cardoso Cruz
Grantee:Caroline Riberti Zaniboni
Supervisor abroad: Ivan Eid Tavares de Araujo
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Local de pesquisa : Icahn School of Medicine at Mount Sinai, United States  
Associated to the scholarship:16/25894-2 - Role of direct and indirect ventral striatal pathways in context-induced reinstatement of alcohol seeking, BP.DR

Abstract

Alcohol is the most used drug around the world and it is related to serious health and social consequences. The AUD (Alcohol Use Disorders) is considered a chronic relapsing disorder characterized by compulsive drug use and seeking despite adverse consequences. In addition, the global consequences of AUS results in millions of annual deaths and economic burden. The neurological disorders of alcohol use is often attributed to its effects on brain circuitry involved in reward system, executive control and withdrawal symptoms. However, ethanol use/misuse can have serious impact on liver, pancreas and gastrointestinal tract. Moreover, the gastrointestinal tract has a communication with the nervous systems, the so-called gut-brain axis. The gut is an important regulator of motivational and emotional processes and it is related with some neuropsychological processes as depression, anxiety and also reinforcement. Hence, this pathway can influence dopamine release in the reward targets of the brain. As example, D1 dopaminergic receptor in medium spine neurons (D1-MSNs) exerts a role in the control of striatum (ventral and dorsal) activities, which is directly related with the reward effects and drug seeking. Despite studies investigating the effects of alcohol on gastrointestinal organs, there is a knowledge gap in literature to explain how alcohol can affects gut microbiota and appetite-regulating hormones. Moreover, since alcohol is a caloric substance (7 kcal/g), we aimed to investigate whether drug seeking can be influence by mechanisms underlying the appetitive pathway of gut-brain axis. Thus, this project aims to understand the role of ventral/dorsal striatum D1 and D2 MSNs in the hedonic/caloric properties of alcohol. Since our primary aim is to investigate the role of ventral striatum D1 and D2 MNS projections on context-induced alcohol seeking, it might be interesting to assess whether alcohol may activate D1 and D2 MSNs by gut-brain axis. To reach this aim, we will investigate the mechanisms underlying post-ingestive and gustatory reward effects of alcohol in the activation of the striatal regions (Ventral versus Dorsal) in different neuronal populations (D1-R versus D2-R). It will be used animal models and operant tasks together with refined tecniques as microdialisys and caspase-mediated ablation of neurons. (AU)