Team 8 – Pharmacology and Addiction Therapies

The current purpose of neurobiological research on psychiatric diseases is to understand the genetic/epigenetic, cellular and molecular mechanisms that mediate the transition from physiological to pathological states. However, when it comes to relapses, in particular after long periods of recovery and abstinence, the international literature is very poor. The activity of our team aims to fill this gap. We are indeed interested in the long-term impact of the exposome at a functional level (receptors, signal transduction, gene profiling, epigenetics regulation) and also by the characterization of peripheral prognostic biomarkers.

To answer our scientific questions, the team is made up of different groups (see illustration). These groups have a specific research focus, but the results obtained are shared between the other groups, enabling mutual enrichment of the research programs.

The addiction group (group leader: Nicolas Marie) aims to develop epigenomic and transcriptomic analysis to identify new therapeutic pathways and biomarkers for monitoring disease progression and therapeutic response. One of the group’s objectives is also to study the pharmacological impact of current clinical treatments on neuroplasticity induced by drugs of abuse (mainly opioids and cocaine). Integrated approaches are used for this purpose.

The co-morbidity group (group leaders: Raymond mongeau, Virginie Beray-Berthat, Claire Leconte): the main aim of this group is to better understand the very high prevalence of co-morbidity between post-traumatic stress disorders (PTSD) and substance abuse. This is crucial, as studies have clearly shown that people suffering from co-occurring disorders have poorer therapeutic outcomes than those suffering from only one type of disorder. New therapeutic strategies must therefore be proposed. Integrated approaches are used for this purpose.

The neuroendocrine signaling axis group comprises two main axes: the Ghrelin system (led by Jacques Pantel) and the CRF system (led by Angelo Contarino). The results obtained clearly demonstrate the involvement of CRF in Substance Use Disorders (SUD). On the other hand there is mounting evidence suggesting that the ghrelin system may serve as a biomarker for assessing pathological states following environmental stressors of a chemical and/or social nature. Both systems may play a key role in relapse, the main problem in clinic. All our results highlight these systems as potential targets for new therapeutic strategies, with druggable targets.

Keywords: addiction, stress, therapeutic targets, biomarkers, behavior, epigenetics

Permanent researchers

Virginie Beray-Berthat, Associate professor, MCU Université Paris Cité, Genetic Epidemiology and functional Genomics of Multifactorial Diseases, Pharmacology and Addiction Therapies
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Loïc Clémenceau, CNRS Research engineer, Cellular homeostasis and cancer, Pharmacology and Addiction Therapies
Angelo Contarino, Associate professor, MCU Université de Bordeaux, Cellular homeostasis and cancer, Pharmacology and Addiction Therapies
Claire Leconte, Associate professor, MCU Université Paris Cité, Pharmacology and Addiction Therapies
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Nicolas Marie, CNRS researcher, CR-CNRS, Cellular homeostasis and cancer, Pharmacology and Addiction Therapies
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Raymond Mongeau, Associate professor, MCU Université Paris Cité, Europe department, Pharmacology and Addiction Therapies
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Florence Noble, CNRS researcher, DR-CNRS, Pharmacology and Addiction Therapies
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Jacques Pantel, INSERM researcher, CR- INSERM, Pharmacology and Addiction Therapies
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Eleni TZAVARA, CNRS researcher, DR-CNRS, Pharmacology and Addiction Therapies

Support staff

Corinne Canestrelli, Inserm Assistant Engineer, Cell death in host-pathogen interactions, Pharmacology and Addiction Therapies
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Post docs and PhD students

Fanny SAULNIER, PhD student, Pharmacology and Addiction Therapies
Derin Reha ULUSOY, PhD Student, Genetic Epidemiology and functional Genomics of Multifactorial Diseases, Pharmacology and Addiction Therapies

Journal articles

2023

ref_biblio: Nicolas Marie, Florence Noble. Oxycodone, an opioid like the others?. Frontiers in Psychiatry, 2023, 14, pp.1229439. ⟨10.3389/fpsyt.2023.1229439⟩. ⟨hal-04767364⟩
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2021

ref_biblio: Geoffroy Goujon, Victor Baldim, Caroline Roques, Nicolas Bia, Johanne Seguin, et al.. Antioxidant activity and toxicity study of cerium oxide nanoparticles stabilized with innovative functional copolymers. Advanced Healthcare Materials, 2021, 10 (11), pp.2100059. ⟨10.1002/adhm.202100059⟩. ⟨hal-03452741⟩
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ref_biblio: Candice Marion, Philippe Zizzari, Raphael G P Denis, Rim Hassouna, Yacine Chebani, et al.. The GhsrQ343X allele favors the storage of fat by acting on nutrient partitioning. Journal of Endocrinology, 2021, pp.JOE-20-0576.R2. ⟨10.1530/JOE-20-0576⟩. ⟨inserm-03365851v2⟩
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ref_biblio: Melissa A Munn-Chernoff, Emma C Johnson, Yi-Ling Chou, Jonathan R.I. Coleman, Laura Thornton, et al.. Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies. Addiction Biology, 2021, 40, pp.e12880. ⟨10.1111/adb.12880⟩. ⟨inserm-02881410⟩
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2020

ref_biblio: Jérôme Busserolles, Ismail Ben Soussia, Laetitia Pouchol, Nicolas Marie, Mathieu Meleine, et al.. TREK1 channel activation as a new analgesic strategy devoid of opioid adverse effects. British Journal of Pharmacology, 2020, 177 (20), pp.4782-4795. ⟨10.1111/bph.15243⟩. ⟨hal-03512213⟩
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2019

ref_biblio: Hélène Geoffroy, Corinne Canestrelli, Nicolas Marie, Florence Noble. Morphine-Induced Dendritic Spine Remodeling in Rat Nucleus Accumbens Is Corticosterone Dependent. International Journal of Neuropsychopharmacology, 2019, 22 (6), pp.394-401. ⟨10.1093/ijnp/pyz014⟩. ⟨hal-02147545⟩
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ref_biblio: Ralf Kuja-Halkola, Joanna Martin, Yi Lu, Christopher Hübel, Catarina Almqvist, et al.. Associations Between Attention-Deficit/Hyperactivity Disorder and Various Eating Disorders: A Swedish Nationwide Population Study Using Multiple Genetically Informative Approaches. Biological Psychiatry, 2019, 86 (8), pp.577-586. ⟨10.1016/j.biopsych.2019.04.036⟩. ⟨hal-02575225⟩
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ref_biblio: Nicolas Marie, Corinne Canestrelli, Florence Noble. Role of pharmacokinetic and pharmacodynamic parameters in neuroadaptations induced by drugs of abuse, with a focus on opioids and psychostimulants. Neuroscience and Biobehavioral Reviews, 2019, 106, pp.217-226. ⟨10.1016/j.neubiorev.2018.06.006⟩. ⟨hal-02147556⟩
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ref_biblio: Florence Noble, Nicolas Marie. Management of Opioid Addiction With Opioid Substitution Treatments: Beyond Methadone and Buprenorphine. Frontiers in Psychiatry, 2019, 9, pp.742. ⟨10.3389/fpsyt.2018.00742⟩. ⟨hal-02147550⟩
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ref_biblio: Hunna Watson, Zeynep Yilmaz, Laura Thornton, Christopher Hübel, Jonathan Coleman, et al.. Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa. Nature Genetics, 2019, 51 (8), pp.1207-1214. ⟨10.1038/s41588-019-0439-2⟩. ⟨hal-02573041⟩
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2018

ref_biblio: Zuzana Hajasova, Corinne Canestrelli, Francine Acher, Florence Noble, Nicolas Marie. Role of mGlu7 receptor in morphine rewarding effects is uncovered by a novel orthosteric agonist. Neuropharmacology, 2018, 131, pp.424-430. ⟨10.1016/j.neuropharm.2018.01.002⟩. ⟨hal-02147571⟩
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ref_biblio: Sophie Lebourgeois, Catherine Vilpoux, Jérôme Jeanblanc, Francine Acher, Nicolas Marie, et al.. Pharmacological activation of mGlu4 and mGlu7 receptors, by LSP2-9166, reduces ethanol consumption and relapse in rat. Neuropharmacology, 2018, 133, pp.163-170. ⟨10.1016/j.neuropharm.2018.01.031⟩. ⟨hal-02147563⟩
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2016

ref_biblio: Yacine Chebani, Candice Marion, Philippe Zizzari, Khadidja Chettab, Marie Pastor, et al.. Enhanced responsiveness of Ghsr Q343X rats to ghrelin results in enhanced adiposity without increased appetite. Science Signaling, 2016, 9 (424), pp.ra39. ⟨10.1126/scisignal.aae0374⟩. ⟨inserm-01463897⟩
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ref_biblio: Marie Garraud, Kahina Khacef, Anne-Clémence Vion, Claire Leconte, Min Yin, et al.. Recombinant tissue plasminogen activator enhances microparticle release from mouse brain-derived endothelial cells through plasmin. Journal of the Neurological Sciences, 2016, 370, pp.187-195. ⟨10.1016/j.jns.2016.09.026⟩. ⟨hal-04709676⟩
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ref_biblio: Marie Garraud, Kahina Khacef, Anne-Clémence Vion, Claire Leconte, Min Yin, et al.. Recombinant tissue plasminogen activator enhances microparticle release from mouse brain-derived endothelial cells through plasmin. Journal of the Neurological Sciences, 2016, 370, pp.187-195. ⟨10.1016/j.jns.2016.09.026⟩. ⟨hal-03367426⟩
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ref_biblio: Magalie Lenoir, Florence Noble. Qu’apporte la neurobiologie aux addictions ?. La Presse Médicale, 2016, 45 (12), pp.1096-1101. ⟨10.1016/j.lpm.2016.02.021⟩. ⟨hal-02347858⟩
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ref_biblio: Luca Posa, Alison Accarie, Florence Noble, Nicolas Marie. Methadone Reverses Analgesic Tolerance Induced by Morphine Pretreatment. International Journal of Neuropsychopharmacology, 2016, 19 (7), pyv108. ⟨10.1093/ijnp/pyv108⟩. ⟨hal-02147576⟩
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2015

ref_biblio: Stéphane Allouche, Thierry Le Marec, Antoine Coquerel, Florence Noble, Nicolas Marie. Striatal dopamine D1 and D2 receptors are differentially regulated following buprenorphine or methadone treatment. Psychopharmacology, 2015, 232 (9), pp.1527-1533. ⟨10.1007/s00213-014-3785-x⟩. ⟨hal-02147637⟩
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ref_biblio: Sandrine Geoffroy, Stéphanie Puig, Nadia Benturquia, Florence Noble. Temporal Regulation of Peripheral BDNF Levels during Cocaine and Morphine Withdrawal: Comparison with a Natural Reward. International Journal of Neuropsychopharmacology, 2015, 18 (5), pyu088 - pyu088. ⟨10.1093/ijnp/pyu088⟩. ⟨hal-01899919⟩
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ref_biblio: Florence Noble, Magalie Lenoir, Nicolas Marie. The opioid receptors as targets for drug abuse medication. British Journal of Pharmacology, 2015, 172 (16), pp.3964-3979. ⟨10.1111/bph.13190⟩. ⟨hal-02147631⟩
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2014

ref_biblio: Stephane Allouche, Florence Noble, Nicolas Marie. Opioid receptor desensitization: mechanisms and its link to tolerance. Frontiers in Pharmacology, 2014, 5, pp.280. ⟨10.3389/fphar.2014.00280⟩. ⟨hal-02149861⟩
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ref_biblio: Corinne Canestrelli, Nicolas Marie, Florence Noble. Rewarding or aversive effects of buprenorphine/naloxone combination (Suboxone) depend on conditioning trial duration. International Journal of Neuropsychopharmacology, 2014, 17 (09), pp.1367-1373. ⟨10.1017/S146114571400025X⟩. ⟨hal-02154084⟩
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ref_biblio: Maria Seleman, Hélène Chapy, Salvatore Cisternino, Cindie Courtin, Maria Smirnova, et al.. Impact of P-glycoprotein at the blood-brain barrier on the uptake of heroin and its main metabolites: behavioral effects and consequences on the transcriptional responses and reinforcing properties. Psychopharmacology, 2014, 231 (16), pp.3139 - 3149. ⟨10.1007/s00213-014-3490-9⟩. ⟨hal-01904771⟩
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2013

ref_biblio: Stéphane Allouche, Thierry Le Marec, Florence Noble, Nicolas Marie. Different patterns of administration modulate propensity of methadone and buprenorphine to promote locomotor sensitization in mice. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2013, 40, pp.286-291. ⟨10.1016/j.pnpbp.2012.10.013⟩. ⟨hal-02154116⟩
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ref_biblio: Fei Teng, Virginie Beray-Berthat, Bérard Coqueran, Clémentine Lesbats, Mélanie Kuntz, et al.. Prevention of rt-PA induced blood–brain barrier component degradation by the poly(ADP-ribose)polymerase inhibitor PJ34 after ischemic stroke in mice. Experimental Neurology, 2013, 248, pp.416-428. ⟨10.1016/j.expneurol.2013.07.007⟩. ⟨hal-02070926⟩
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2012

ref_biblio: Stéphanie Puig, Florence Noble, Nadia Benturquia. Short- and long-lasting behavioral and neurochemical adaptations: relationship with patterns of cocaine administration and expectation of drug effects in rats. Translational Psychiatry, 2012, 2 (10), pp.e175 - e175. ⟨10.1038/tp.2012.103⟩. ⟨hal-01899921⟩
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2011

ref_biblio: Cynthia Marie-Claire, Thierry Le Marec, Cynthia Marie, Florence Noble, Nicolas Marie. Chronic and intermittent morphine treatment differently regulates opioid and dopamine systems: a role in locomotor sensitization. Psychopharmacology, 2011, 216 (2), pp.297 - 303. ⟨10.1007/s00213-011-2223-6⟩. ⟨hal-01905192⟩
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2009

ref_biblio: Vanessa Brochard, Béhazine Combadière, Annick Prigent, Yasmina Laouar, Aline Perrin, et al.. Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease.. Journal of Clinical Investigation, 2009, 119 (1), pp.182-92. ⟨10.1172/JCI36470⟩. ⟨inserm-00393947⟩
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ref_biblio: Jacques Pantel, Marie Legendre, Sylvie Nivot, Séverine Morisset, Marie Vie-Luton, et al.. Recessive Isolated Growth Hormone Deficiency and Mutations in the Ghrelin Receptor. Journal of Clinical Endocrinology and Metabolism, 2009, 94 (11), pp.4334-4341. ⟨10.1210/jc.2009-1327⟩. ⟨hal-02081574⟩
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2008

ref_biblio: Stephane Desjardins, Emilie Belkai, Dominique Crete, Laurie Cordonnier, Jean-Michel Scherrmann, et al.. Effects of chronic morphine and morphine withdrawal on gene expression in rat peripheral blood mononuclear cells. Neuropharmacology, 2008, 55 (8), pp.1347 - 1354. ⟨10.1016/j.neuropharm.2008.08.027⟩. ⟨hal-01905201⟩
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ref_biblio: Sabah Kelai, Gilles Maussion, Florence Noble, Claudette Boni, Nicolas Ramoz, et al.. Nrxn3 upregulation in the globus pallidus of mice developing cocaine addiction.. NeuroReport, 2008, 19 (7), pp.751-5. ⟨10.1097/WNR.0b013e3282fda231⟩. ⟨inserm-00320209⟩
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2004

ref_biblio: Cynthia Marie-Claire, Cindie Courtin, Bernard P. Roques, Florence Noble. Cytoskeletal genes regulation by chronic morphine treatment in rat striatum.. Neuropsychopharmacology, 2004, 29 (12), pp.2208-15. ⟨10.1038/sj.npp.1300513⟩. ⟨inserm-00144800⟩
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1997

ref_biblio: Bruno Bellier, Isabelle Mccort, Bertrand Ducos, Sophie Danascimento, Hervé Meudal, et al.. Synthesis and Biological Properties of New Constrained CCK-B Antagonists: Discrimination of Two Affinity States of the CCK-B Receptor on Transfected CHO Cells. Journal of Medicinal Chemistry, 1997, 40 (24), pp.3947-3956. ⟨10.1021/jm970439a⟩. ⟨hal-02122116⟩
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ref_biblio: Florence Noble, Claire Smadja, Olga Valverde, Rafael Maldonado, Pascale Coric, et al.. Pain-suppressive effects on various nociceptive stimuli (thermal, chemical, electrical and inflammatory) of the first orally active enkephalin-metabolizing enzyme inhibitor RB 120. Pain, 1997, 73 (3), pp.383-391. ⟨10.1016/S0304-3959(97)00125-5⟩. ⟨hal-02461424⟩
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1996

ref_biblio: Jean-Jacques Remy, Laurence Couture, Jacques Pantel, Thomas Haertlé, Hanitra Rabesona, et al.. Mapping of HCG-receptor complexes. Molecular and Cellular Endocrinology, 1996, 125 (1-2), pp.79-91. ⟨10.1016/S0303-7207(96)03955-X⟩. ⟨hal-03141890⟩
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1994

ref_biblio: Florence Noble, Pascale Coric, Serge Turcaud, Marie-Claude Fournie-Zaluski, Bernard P. Roques. Assessment of physical dependence after continuous perfusion into the rat jugular vein of the mixed inhibitor of enkephalin-degrading enzymes, RB 101. European Journal of Pharmacology, 1994, 253 (3), pp.283-287. ⟨10.1016/0014-2999(94)90203-8⟩. ⟨hal-02461489⟩
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1992

ref_biblio: Marie Claude Fournie-Zaluski, Pascal Coric, Serge Turcaud, Evelyne Lucas, Florence Noble, et al.. Mixed-inhibitor-prodrug as a new approach toward systemically active inhibitors of enkephalin-degrading enzymes. Journal of Medicinal Chemistry, 1992, 35 (13), pp.2473-2481. ⟨10.1021/jm00091a016⟩. ⟨hal-02461535⟩
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ref_biblio: Marie Claude Fournie-Zaluski, Pascale Coric, Serge Turcaud, Luce Bruetschy, Evelyne Lucas, et al.. Potent and systemically active aminopeptidase N inhibitors designed from active-site investigation. Journal of Medicinal Chemistry, 1992, 35 (7), pp.1259-1266. ⟨10.1021/jm00085a013⟩. ⟨hal-02461529⟩
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ref_biblio: Florence Noble, Pascale Coric, Marie-Claude Fournie-Zaluski, Bernard P. Roques. Lack of physical dependence in mice after repeated systemic administration of the mixed inhibitor prodrug of enkephalin-degrading enzymes, RB101. European Journal of Pharmacology, 1992, 223 (1), pp.91-96. ⟨10.1016/0014-2999(92)90822-L⟩. ⟨hal-02461500⟩
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Reports

2012

ref_biblio: Agnès Cadet-Taïrou, Tiphaine Canarelli, Serge Escots, Françoise Facy, Laurence Lanfumey-Mongredien, et al.. Médicaments psychotropes : Consommations et pharmacodépendances. [Rapport de recherche] Institut national de la santé et de la recherche médicale(INSERM). 2012, Paris : Inserm : Éditions EDP Sciences (ISSN : 1264-1782) / 598 p. ⟨inserm-02102985⟩
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Preprints, Working Papers, ...

2021

ref_biblio: Magalie Lenoir, Isabella Bondi, Loïc Clemenceau, Isabelle Nondier, Margaux Ballé, et al.. Inhibition of striatal SEZ6 by miR-3594-5p is a drug-specific marker for late-stage heroin intake escalation. 2021. ⟨hal-03365414⟩
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