Investigation of the Molecular Mechanisms Involved in the Interaction between Ethanol and Cocaine in a Simultaneous Self-Administration Model in Rats: A Metabolomic Study of the Accumbens Nucleus

• Grant number: 24/04202-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: October 01, 2024
• End date: March 31, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Fabio Cardoso Cruz
• Grantee: Giovanna Victória Lopes Costa
• 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

The consumption of multiple psychoactive substances is a common phenomenon, particularly prevalent among those grappling with substance use disorders. Among the most concerning combinations is the simultaneous use of cocaine and alcohol, a mixture that enhances the euphoric effects of cocaine while mitigating its adversities. Despite the prevalence of this consumption pattern, its repercussions remain largely enigmatic, with preclinical literature predominantly focusing on the effects of the isolated use of these substances, leaving a gap in understanding simultaneous consumption, especially in animal models reflecting motivation in seeking these drugs. In this scenario, the present study aims to fill this critical gap by proposing the standardization of an animal model of simultaneous alcohol and cocaine use in rats and correlating it with alterations in the metabolome of the nucleus accumbens, one of the main brain regions where interaction between these drugs can occur. To achieve this, adult male rats will undergo an operant self-administration protocol of cocaine and/or ethanol consisting of (i) behavioral acquisition, (ii) self-administration training with alcohol and/or cocaine, (iii) simultaneous self-administration, and (iv) binge. Upon completion of the behavioral experiment, the animals will be anesthetized and euthanized, and their brains will be used for metabolomic analysis of the nucleus accumbens (experiment 1), or their perfused brains will be allocated for immunofluorescence technique to quantify the types of activated cells during isolated or combined ethanol and cocaine consumption (experiment 2). This project will help understand the neurobiological aspects involved in the concurrent cocaine and alcohol consumption, offering the potential for future investigations into targeted interventions and therapies.