PhD Scholarship

Title of the subject: Mechanisms involved in compulsive behaviors related to drug addiction

Keywords: Drug addiction, behavior, punishment, motivation, neurobiology, endogenous cannabinoid system, brain circuitry

Abstract:

Drug addiction is characterized by excessive substance use despite negative health consequences. This project focuses on the underlying mechanisms of compulsive behaviors related to addiction, using a newly developed punishment procedure in rats (Desmercieres et al., 2022). The objectives are to adapt this procedure to cocaine self-administration, to study the relationship between punishment resistance for food and cocaine, and to analyze the brain mechanisms involved in this resistance. The project combines behavioral and molecular approaches to study the underlying neurobiological mechanisms.

Context and problem statement:

Research on addiction has long focused on motivational and reward processes. However, understanding the behavioral and biological mechanisms that maintain drug use despite negative consequences is crucial. This project aims to examine these mechanisms using a punishment procedure to study compulsive drug-related behaviors.

Subject description:

We hypothesize that punishment resistance will remain stable for food but will progressively increase for cocaine. This increase in loss of control will be observed in a minority of vulnerable individuals. Furthermore, we propose that punishment resistance is associated with changes in gene expression of the endocannabinoid system (ECS), particularly in the striatum and insular cortex. This knowledge is crucial for developing more effective therapies against addiction.

Methodology and implementation:

The project combines behavioral techniques with molecular approaches to study the neurobiological mechanisms of punishment resistance. We will use drug self-administration techniques adapted to the new punishment procedure. Molecular biology methods such as RT-PCR and pyrosequencing will be used to study changes in gene expression associated with compulsive behaviors. Viral approaches could be used to manipulate gene expression and test their causal involvement in addiction.