Neuropharmacology of peptidergic systems; opioid and anti-opioid systems; G protein-coupled receptor signaling and regulation; stress-related memory disorders.
I have been studying the pharmacology of opioid and anti-opioid (nociceptin/orphanin FQ or N/OFQ, neuropeptide FF) systems for several years at the molecular (receptor architecture and post-translational modifications), cellular (proteomics of cell signaling) and behavioral level (pain, addiction).
My current main project in the REMEMBeR team is focused on the characterization of the contribution of the N/OFQ system to normal and pathological memory. On one side we evaluate the ability of N/OFQ analogues to attenuate emotional memories in various paradigms in mouse (fear conditioning, conditioned place preference). On the other side we test the ability of antagonists of the N/OFQ receptor to improve hippocampus dependent memory in mouse models of stress-related cognitive dysfunction. Behavioral approaches are combined with neurochemical and cellular analyses to better understand the mechanisms that underlie memory regulation by the N/OFQ system.
In parallel I contribute to other projects developed by members of the REMEMBeR team: adult neurogenesis in neurodegenerative diseases (C Rampon), chronic stress and depression (B Guiard)…
M.-C. Miquel, CRCA, Toulouse, Fr
L. Casteilla, STROMAlab, Toulouse, Fr
S. Schulz, Institute of Pharmacology and Toxicology, University of Jena, Germany.
G. Calo, C. Ruzza, Department of Medical Sciences, University of Ferrara, Italy
N. Zaveri, Astraea Therapeutics, USA
Selected recent publications:
L. Moulédous, 2019, The nociceptin/orphanin FQ system and the regulation of memory. Handbook of Experimental Pharmacology. 254:259-278
L. Moulédous, P. Roullet, and B.P. Guiard, 2018, Brain Circuits Regulated by the 5-HT2A Receptor: Behavioural Consequences on Anxiety and Fear Memory. In 5-HT2A Receptors in the Central Nervous System, Guiard, BP, and Di Giovanni, G, Eds., series “The receptors”, Springer, vol. 32, pp. 231-258.
K. Rekik, R. Faria Da Silva, M. Colom, S. Pacifico, N.T. Zaveri, G. Calo', C. Rampon, B. Frances, and L. Moulédous, 2017, Activation of nociceptin/orphanin FQ receptors inhibits contextual fear memory reconsolidation. Neuropharmacology. 125:39-49.
L. Moulédous, C. Froment, O. Burlet-Schiltz, S. Schulz S, and C. Mollereau, 2015, Phosphoproteomic analysis of the mouse brain mu-opioid (MOP) receptor. FEBS Letters. 589(18):2401-8.
A. Gomez-Brouchet, N.Blaes, L. Moulédous, O. Fourcade, I. Tack, B. Francès, J.P. Girolami, and V. Minville, 2015, Beneficial effects of levobupivacaine regional anaesthesia on postoperative opioid induced hyperalgesia in diabetic mice. Journal of Translational Medicine. 13:208.
N. Massaly, B. Francés, and L. Moulédous, 2015, Roles of the ubiquitin proteasome system in the effects of drugs of abuse. Frontiers in Molecular Neuroscience. 7:99.
L. Bray, C. Froment, P. Pardo, C. Candotto, O. Burlet-Schiltz, J.M. Zajac, C. Mollereau, and L. Moulédous, 2014, Identification and Functional Characterization of the Phosphorylation Sites of the Neuropeptide FF2 Receptor. Journal of Biological Chemistry. 289(49):33754-66.
K. Carayon*, L. Moulédous*, A. Combedazou, S. Mazères, E. Haanappel, L. Salomé, and C. Mollereau, 2014, Heterologous Regulation of mu-opioid (MOP) Receptor Mobility in the Membrane of SH-SY5Y Cells. Journal of Biological Chemistry. 289(41):28697-706.
L. Glück, A. Loktev, L. Moulédous, C. Mollereau, P.Y. Law, and S. Schulz, 2014, Loss of Morphine Reward and Dependence in Mice Lacking G Protein-Coupled Receptor Kinase 5. Biological Psychiatry. 76(10):767-74.
N. Massaly, L. Dahan, M. Baudonnat, C. Hovnanian, K. Rekik, M. Solinas, V. David, S. Pech, J-M. Zajac, P. Roullet, L. Moulédous*, and B. Frances*, 2013, Involvement of protein degradation by the ubiquitin proteasome system in opiate addictive behaviors, NeuroPsychoPharmacology, 38(4):596-604.
S. Grastilleur, L. Moulédous, J. Bedel, J. Etcheverry, M. Bader, J.P. Girolami, O. Fourcade, B. Frances, and V. Minville, 2013, Role of kinin B2 receptors in opioid-induced hyperalgesia in inflammatory pain in mice, Biological Chemistry, 394(3):361-8.
K. Elhabazi, J. Trigo, C. Mollereau, L. Moulédous, J.M. Zajac, F. Bihel, M. Schmitt, J. Bourguignon, H. Meziane, B. Petit-Demoulière, F. Bockel, R. Maldonado, and F. Simonin, 2012, Involvement of neuropeptide FF receptors in neuroadaptative responses to acute and chronic opiate treatments. British Journal of Pharmacology, 165(2):424-35.
L. Moulédous, C. Froment, S. Dauvillier, O. Burlet-Schiltz, J.M. Zajac, and Mollereau C, 2012, GRK2 Protein-mediated transphosphorylation contributes to loss of function of μ-opioid receptors induced by Neuropeptide FF (NPFF2) Receptors. Journal of Biological Chemistry. 287(16):12736-12749.