Our research project focuses on the phase of abstinence in addiction as a window of opportunity for therapeutic interventions. Indeed, it has been proposed that repeated drug administrations cause deregulations involved in reward, cognitive and stress processes. Our working hypothesis is that environmental and pharmacological manipulations can reverse these deregulations or reverse neuroadaptation. Consequently it will reduce the risk of relapse.
We combine behavioral, neurochemical, electrophysiological and molecular expertise to lead to a better understanding of neuroadaptations induced by repeated exposures to persistent drugs. Next, we use this knowledge to develop new therapeutic strategies to treat drug dependence.
Our research project has 3 main axes: 1) research of sustainable neuroadaptations induced by the excessive drug intake; 2) behavioral and neurobiological mechanisms involved in the positive effects of the enriched environment (EE) against dependence; 3) the discovery and characterization of molecular mechanisms mimicking the EE effects (environment-mimetics) in order to develop new pharmacological tools to treat addiction.
For these axes, we have 4 levels of investigation
The behavioral characterization of the effects of our manipulations on addiction parameters
Characterization of the effects of our manipulations on cognitive, emotional and stress response
Characterization of neurobiological mechanisms underlying behavioral observations
The use of different invasive approaches (lesions, injections of pharmacological products, viral approaches, DREADDs, etc.) in specific regions of the brain to confirm in vivo the causal implication of the identified mechanisms in addiction.
In addition, thanks to the presence of clinicians in our team working on drug dependence at the Poitiers hospital, an ultimate step in our research may be to test in humans the effectiveness of our new therapies.
Figure 1- The curative effects of the enriched environment or pharmacological treatments within the framework of the allostatic hypothesis of addiction. In this hypothesis, repeated exposures to drugs lead to a shift from the initial hedonic level (horizontal black line) to a lower allostatic level (red line) in which individuals will be exposed to drugs and unable to resist the lack of drugs. When an individual is addicted, chronic therapeutic interventions would gradually increase the hedonic point whereas this hedonic point for untreated patients would remain low for long periods (red line).
Figure 2 –a) enriched environment in mice; b) cage of “conditioned place preference”; c) Enriched environment in the rat. Photos submitted to CNRS Copyright.
Marcello Solinas – CPER/FEDER, HaBiSan- Etude des déficits comportementaux et neurobiologiques associés à l’addiction aux drogues chez des animaux hébergés en milieu semi-naturel; 2017-2020; 364k€
Nathalie Thiriet – Fondation pour la recherche en alcoologie 2 X 8K€
Marcello Solinas- Fondation Recherche Medicale (FRM) Special Call “Physiopathology of addiction”, Project Title: “Effects of Environmental Enrichment on cocaine-induced alterations in brain metabolic activity” 2014-2017, Amount: 200 K€
Pauline Belujon -Agence National de la Recherche (ANR), ANR JC, , “Role of the amygdala-insular cortex circuit in the persistent risk of relapse”, 2015, 260 K€
Marcello Solinas – Fondation de l’Avenir, Translational Medicine Projet “ADDICSTATINE: Randomized double blind, placebo controlled trial of the efficacy of simvastatin for smoking cessation”, 2014, 50 K€