Team 2 : Neurobiology and Neuropharmacology of Addiction

Summary of the research project 

The main focus of our research project is the protracted abstinence/relapse phase of addiction as a window of opportunity for therapeutic intervention. It has been hypothesized that chronic administration of drugs leads to dysregulation of brain systems involved in reward, cognitive and stress processes. Our working hypothesis is that environmental or pharmacological manipulations can reverse or counteract these neuroadaptations and consequently reduce the risks of relapse. We combine behavioral, neurochemical, electrophysiological and molecular skills present in our laboratory to provide better understanding of the persistent neuroadaptations induced by repeated exposure to drug and to provide novel therapeutic strategies to cure drug addiction. Our research project has three main axes: 1) the characterization of the neurobiological “traces” produced by chronic exposure to drugs; 2) the investigation of the positive effects of environmental enrichment (EE) on drug addiction; and 3) the discovery and characterization of molecules that mimic the effects of EE or “environmimetics” to treat drug addiction. For each of these axes, we have three levels of investigation i) the behavioral characterization of the effects of our manipulations on measures of drug addiction; ii) the characterization of the effects of our manipulations on cognitive functions and emotional responses and iii) the characterization of neurobiological mechanisms underlying our behavioral observations. Provided that potential interesting mechanisms are discovered, a fourth level of analysis will consist in the direct manipulation of this mechanism by intracranial injection or viral vector to confirm the in vivo validity of our hypothesis. Thanks to the presence in our team of clinicians working on drug dependence in the local Poitiers Hospital, a final step of our research may be the test in humans of the effectiveness of the potential new medications

Fig. 1. Curative effects of environmental enrichment or pharmacological treatments in the framework of the allostasis hypothesis of addiction. According to this hypothesis, repeated exposure to drugs results in the shift of an initial hedonic (black horizontal line) point to a lower allostatic point (red line) in which individuals would be enslaved to the drug and incapable of resisting drug craving. Once an individual is addicted, chronic therapeutic intervention would slowly increase the hedonic set-point toward the pre-drug level (blue line) whereas the hedonic set-point of non-treated individuals would stay low for long periods of time (red line).

Fig. 1. Curative effects of environmental enrichment or pharmacological treatments in the framework of the allostasis hypothesis of addiction. According to this hypothesis, repeated exposure to drugs results in the shift of an initial hedonic (black horizontal line) point to a lower allostatic point (red line) in which individuals would be enslaved to the drug and incapable of resisting drug craving. Once an individual is addicted, chronic therapeutic intervention would slowly increase the hedonic set-point toward the pre-drug level (blue line) whereas the hedonic set-point of non-treated individuals would stay low for long periods of time (red line).

 

ENV1 ENV2

Fig. 2. Environmental enrichment in mice and rats.

Publications

Fundings

IREB 2013

Fondation de la Recherche Medicale 2014

Fondation de l’Avenir (2014)

Co-financement Region Poitou-Charentes 2014

ANR JC; PI: P. Belujon

funding1 funding2 funding3 funding4

 

 

Recherche

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