Addiction is a worldwide public health problem for which there are currently no satisfactory treatments. The originality of our own research is to focus mainly on treatments and relapse, which is the main problem in clinic, and constitutes a completely under explored scientific field in basic research. In that purpose, we are using multidisciplinary approaches ranging from molecular and cellular biology to behavioral studies, and vice versa.
It is now well established that a combination of factors influences risks for addiction: biological factors, environmental factors and neuroadaptations induced by drugs. All these factors play a role in long-lasting neuroplasticity. To decipher these cellular and molecular mechanisms involved in this risk and especially in the vulnerability to relapse, we are investigating the neuroadaptations induced by drugs of abuse following prolonged exposure and after withdrawal. Our main goal is to achieve a better understanding of the long-term neuroadaptations induced by drugs of abuse, allowing to characterize those involved in vulnerability to relapse, in order to propose either new therapeutic strategies, or to refine current treatments.
We are also investigating neurochemical balances known to be altered during withdrawal and relapses. Using pharmacological tools (agonists and antagonists) we are investigating the role of some neurotransmitter systems in relapse induced by different factors. Among these factors, we have already demonstrated the importance of temporal factors, and reexposure to low doses of drugs of abuse. Using animal models of stress (trauma, social, metabolic), the team is also investigating the cellular and molecular links between stress/addiction/relapse. Finally, using a genetic model in rat we are studying how the sensitivity to a peripheral hormone influenced by nutritional status and stress, grhelin, may influence the development and relapse to an addictive behavior.
- Morphine-Induced Dendritic Spine Remodeling in Rat Nucleus Accumbens Is Corticosterone Dependent.
Geoffroy H, Canestrelli C, Marie N, Noble F : Int J Neuropsychopharmacol, 2019
Marie N., Canestrelli C. and Noble F. (2018) Role of pharmacokinetic and pharmacodynamic parameters in neuroadaptations induced by drugs of abuse, with a focus on opioids and psychostimulants. Neuroscience and Biobehavioral Reviews.
Hajasova Z, Canestrelli C, Acher F, Noble F, Marie N. (2018) Role of mGlu7 receptor in morphine rewarding effects is uncovered by a novel orthosteric agonist. Neuropharmacology.
Posa L, Accarie A, Noble F, Marie N. (2016) Methadone Reverses Analgesic Tolerance Induced by Morphine Pretreatment. Int J Neuropsychopharmacol.
Chebani Y, Marion C, Zizzari, P, Chettab K, Pastor M, Korostelev M, Geny D, Epelbaum J, Tolle V, Morisset S and Pantel J. (2016) Enhanced responsiveness of GhsrQ343X rats to ghrelin results in enhanced adiposity without increased appetite.
Martin V, Riffaud A, Marday T, Brouillard C, Franc B, Tassin JP, Sevoz-Couche C, Mongeau R, Lanfumey L. (2017) Response of Htr3a knockout mice to antidepressant treatment and chronic stress. Br J Pharmacol.