Evaluation of the Potentialization of the Reinforcing Effect of Cocaine by MDMB-4en-PINACA and Impacts on the Dopaminergic System of Mice

• Grant number: 24/15870-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2024
• End date: October 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Fabio Cardoso Cruz
• Grantee: Mariana Lima dos Santos
• 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 use of illicit substances, especially cocaine, has become a growing problem worldwide. Data from UNODC (2023) indicate that, in 2021, were approximately 296 million drug users, a significant increase compared to previous years. Cocaine, in particular, is a stimulant drug that has a high potential for dependence and is often associated with serious physical and mental health problems. The concomitant use of synthetic cannabinoids, such as MDMB-4en-PINACA, with stimulant drugs has been linked to an increased toxicity and risk of dependence. This study aims to contribute to the understanding of the neurobiological mechanisms underlying these effects, exploring the hypothesis that co-administration of MDMB-4en-PINACA may increase the reinforcing effect of cocaine, mediated by changes in the mesocorticolimbic dopaminergic system. The project overall objectives include the evaluation of the reinforcing property of the synthetic cannabinoid MDMB-4en-PINACA, both alone and in combination with cocaine, and the analysis of its impact on the dopaminergic neurotransmission system. For this purpose, we will use male C57/Bl6 mice, which will be submitted to the conditioned place preference (CPP) protocol induced by the administration of MDMB-4en-PINACA alone and associated with cocaine. After the CPP test, the animals will be euthanized and the brains collected to quantify the concentrations of dopamine and its metabolites in specific brain regions, such as the prefrontal cortex, nucleus accumbens and dorsal striatum, using the high-performance liquid chromatography (HPLC) technique. The statistical analysis will include tests of normality, homogeneity and sphericity, using multifactorial ANOVA and the Tukey post-hoc test, with a significance level set at p<0.05. The results of this study are expected to provide valuable information on the interaction between MDMB-4en-PINACA and cocaine, contributing to the understanding of the neurobiological mechanisms that may be involved in the increased reinforcing effect of cocaine caused by concomitant use with MDMB-4en-PINACA. Furthermore, the research may help to elucidate the risks associated with the concomitant use of these substances, providing a basis for future investigations and clinical interventions.