Lieu : Salle de conférence du Neurocentre Magendie
Thèse dirigée par Véronique Deroche (Neurocentre Magendie)
Soutenance en anglais
Titre
Psychobiological Mechanisms of Maladaptive Cocaine Seeking
Abstract
About 20% of cocaine users suffer with severe cocaine use disorder (CUD) or addiction, and to date, there are limited therapeutic options available. Due to this, there is an increased need to focus on the neurobiology surrounding key behavioral features of cocaine use disorder.
My thesis focuses on understanding the psychobiological mechanisms of the emergence of maladaptive seeking- a key behavioral feature in those who suffer from CUD. Within my research, I use a model of CUD in the rat previously pioneered by our lab and acknowledged as a breakthrough in the field. In this model, 15% of rats develop an addiction-like behavior after protracted intravenous self-administration (SA). Critically, after early cocaine SA, a maladaptive seeking behavior emerges that is reliably predictive of the transition to addiction.
The factors influencing the emergence of this maladaptive seeking behavior are explored in this manuscript.
Combining behavioral methods, analytical chemistry and calcium imaging, I study the psychopharmacological and neurobiological determinants of this early maladaptive seeking behavior. I hypothesized and demonstrated that early maladaptive seeking results from an increased control of behavior by incentive internal cues at the expense of control by adaptive inhibitory external cues, which is related to altered recruitment of the prelimbic cortex (PL). Addiction is a relapsing disorder with 80% of users failing at remaining abstinent, making relapse a major clinical challenge. Therefore, I focused on how the mechanisms identified in the first two objectives modulate relapse, modeled in rats using the reinstatement procedure.
This PhD work explores and identifies crucial psychopharmacological mechanisms that are involved in a key behavioral characteristic of the transition to addiction: maladaptive seeking. In addition, it detects neurobiological correlates of predictive markers of the vulnerability to addiction. Consequently, it sets an early foundation to explore potential treatment modalities that piggyback off of the psychopharmacological or neurobiological differences discovered.
Keywords: cocaine use disorder, self-administration, vulnerability, animal model, prelimbic cortex, fiber photometry, outbred rats
Jury
Mme Véronique DEROCHE – Université de Bordeaux – Directrice de thèse
Mme Stéphanie CAILLÉ-GARNIER – Université de Bordeaux – Examinatrice
M. Mickaël NAASSILA – Université de Picardie Jules Verne – Rapporteur
Mme Pauline BELUJON – Universite de Poitiers – Examinatrice
Mme Elena MARTIN-GARCIA – Université de Barcelone / PRBB – Examinatrice
Mme Anne-Noël SAMAHA – Université de Montréal – Rapporteure