I cannot stop after the first ‘drink’! Alcohol effects on the inhibitory control brain systems

• Grant number: 19/01686-0
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: September 01, 2019
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Karina Possa Abrahão
• Grantee: Karina Possa Abrahão
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant(s): 19/22009-6 - Multi-User Equipment approved in grant 2019/01686-0: patch clamp setup (electrophysiology), AP.EMU; 19/22011-0 - Multi-User Equipment approved in grant 2019/01686-0: photometry setup, AP.EMU
• Associated scholarship(s): 24/06625-7 - Electrophysiological characterization of the internal neuronal network of the External Globus Pallidum: brain region involved in decision making, BP.MS; 24/00813-6 - Just one more "drink" and I swear I will stop! The effects of alcohol on behavior, BP.JC; 24/00814-2 - Just one more "drink" and I swear I will stop! The effects of alcohol on behavior, BP.JC; + associated scholarships 22/15972-7 - The impact of age on the electrophysiomolecular characteristics and pharmacological effects of ethanol on GABAergic neurons of the external globus pallidus, BP.DR; 23/16063-3 - Software usage for lickometer data analysis, BP.TT; 23/02004-5 - The effects of puerarin on anxiety-like behavior and its relationship to ethanol consumption, BP.MS; 21/09927-6 - How diets rich in isoflavone alter the drinking pattern of ethanol, BP.IC; 20/12260-0 - The effects of alcohol on the direct pathway of dorsal striatum sub-regions: a central component in decision-making, BP.DR; 20/06214-6 - Impact of the alcoholic intoxication in adolescence on ethanol consumption and inhibitory control in adult life: participation of the arkypallidal pathway, BP.MS; 19/24650-0 - Study about the interaction of food and alcohol consumption, BP.IC - associated scholarships

Abstract

Decades of scientific studies have collected data on how alcohol (ethanol) can affect the brain. The development of new technologies has made possible the study of the effects of alcohol in specific brain pathways that are associated with the most diverse physiological functions. The lack of control over ethanol consumption is one of the main characteristics of the binge drinking and the relapse during abstinence. However, few studies have focused on how ethanol interferes with the brain sys-tems of inhibitory control. We hypothesized that ethanol itself alters the function of neuronal sys-tems of decision-making and inhibitory control to affect the ability to self-control. To that end, we will study the pattern (microstructure) of ethanol consumption by C57Bl/J6 mice (natural drinkers of high amounts of ethanol) and Swiss mice (outbred mice for the study of behavioral variability), males and females, which will allow a better understanding about the characteristics of the uncon-trolled ethanol consumption. In addition, we will study the physiological effects of ethanol on the synaptic activity of brain regions that are part of the inhibitory control system: cortex and subtha-lamic nucleus, subthalamic nucleus and globus pallidus; and globus pallidus and striatum. Using the Cre-Flox transgenic system, we will use photometry of Ca2+ activity (GCaMP protein) to measure the activity of specific synaptic boutons; and electrophysiology (patch clamp and optogenetics) to measure synaptic activity of each of the synapses of the regions mentioned above. Finally, we will use the chemogenetic (DREADDs) to artificially mimic the effects of ethanol observed in the pho-tometry and electrophysiology experiments. This will allow us to manipulate the specific pathway of the brain in vivo and observe the behavioral consequences (ethanol consumption with the protocol studied in the first stage of this project) of each of the ethanol's effect on the inhibitory control brain systems. The findings of this project will allow a broad understanding of maladaptation of decision making and inhibitory control, which may help in the development of better interventions for patients with problems associated with alcohol use disorders. In addition, the results will help to better understand the brain pathways associated with other neurological and psychiatric diseases. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CAMARGO EDUARDO, PAULA MENDONCA; ABRAHAO, KARINA POSSA. ood composition can influence how much alcohol your animal model drinks: A mini-review about the role of isoflavone. ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, v. 46, n. 1, NOV 2021. (19/01686-0, 19/24650-0)

CECYN, MARIANNA NOGUEIRA; ABRAHAO, KARINA POSSA. Where do you measure the Bregma for rodent stereotaxic surgery?. IBRO NEUROSCIENCE REPORTS, v. 15, p. 6-pg., 2023-12-01. (19/01686-0)