Serotonin signaling in plasticity and disease

Leader

Research center

17 rue du Fer à Moulin
75005 Paris

Institution

Inserm
Université Pierre et Marie Curie
ED158
Université Pierre et Marie Curie

Laboratory

Marianne Coutures
Phone: 01 45 87 61 35
UMRS 839

Mots clefs

addiction
dopamine
impulsivity
serotonin
 

publications

Diaz, SL, Doly, S, Narboux-Nême, N, Fernandez, S, Mazot, P, Banas, SM, Boutourlinsky, K, Moutkine, I, Belmer, A, Roumier, A, and Maroteaux, L, 5-HT2B receptors are required for serotonin-selective antidepressant actions Molecular Psychiatry 2012 Feb;17(2):154-63. 

Ebrahimkhani M, Oakley F, Murphy L, Mann J, Moles A, Perugorria M, Ellis E, Burt A, Douglass A, Wright M, White S, Jaffré F, Maroteaux L, Mann D. Stimulating healthy tissue regeneration by targeting the 5-HT2B receptor in chronic liver disease. Nature Medicine. 2011 Nov 27;17(12):1668-73. 

Banas SM, Doly S, Boutourlinsky K, Diaz SL, Belmer A, Callebert J, Collet C, Launay JM, Maroteaux L. Deconstructing Antiobesity Compound Action: Requirement of Serotonin 5-HT2B Receptors for Dexfenfluramine Anorectic Effects. Neuropsychopharmacology. 2011 Jan;36(2):423-33.

Bevilacqua, L., Doly, S., Kaprio, J., Yuan, Q., Tikkanen, R., Paunio, T., Zhou, Z., Wedenoja, J., Maroteaux, L, Diaz, S., Belmer, A., Hodgkinson, C., Dell’Osso, L., Suvisaari, J., Coccaro, E., Rose, R., Peltonen, L., Virkkunen, M., and Goldman, D. A population-specific stop codon in the HTR2B gene co-segregates with severe impulsivity. Nature 2010 Dec;468(8):1061-1066. 

Doly S, Valjent E, Setola V, Callebert J, Hervé D, Launay JM, Maroteaux L. Serotonin 5-HT2B receptors are required for 3,4-methylenedioxymethamphetamine-induced hyperlocomotion and 5-HT release in vivo and in vitro. J Neurosci. 2008 Mar 12;28(11):2933-40.

Fields of research

Neuropharmacology / cell signaling

Research Theme

Our present work started from our observation that serotonin tone can be controlled by a feed-forward mechanism via 5-HT2B receptors. Recent independent investigations and our unpublished results indicate that this same serotonergic receptor may also impact local dopamine levels. The absence of 5-HT2B receptors, DA-targeting drugs induce a reduced increase in extracellular DA in NAcc, but a normal increase in dorsal striatum, thus an imbalance that could underlie addictive behaviors. Other unpublished evidence (in collaboration with D. Goldman, NIH) indicates that 5-HT2B receptor haplotypes, which correspond to lower expressing individuals, segregate with cocaine abuser. These data support again in Humans our finding in mice that this receptor inactivation is favoring addictive behaviors. Recent independent investigations, and our unpublished results indicate a control of microglia by serotonin, but its potential physiological implications has never been investigated. Our preliminary data indicate that microglia express mainly one type of numerous serotonin receptors, the 5-HT2B, which had not been studied before. Our work now intends to unravel links between serotonin and dopamine system in relation to impulsivity, compulsivity and addiction and to identify the cellular basis of these actions (dopamine and/or serotonin neurons and/or microglia).

Membres de l'équipe

ROUMIER Anne
MOUTKINE Imane
DIAZ Silvina
BANAS Sophie
KOLODZIEJCZA Marta
QUENTIN Emily
SANDULACHE Miriam

Lab rotation

Serotonin and microglia

Chercheur responsable: 

MAROTEAUX Luc

Dates: 

1 January 2017 - 30 June 2017

Date limite de candidature: 

1 April 2016

Lab rotation proposal

~ Jan-March 2017 ~ Apr-June 2017

Project:

Htr2b encodes the main serotonin receptor expressed by microglial cells. Microglia have been recently involved in several psychiatric disorders, and we observed that lack of Htr2b receptor leads to increased vulnerability to sickness behavior induced by peripheral inflammation, a state that shares some aspects with depression. Thus, unraveling the mechanisms sustaining this vulnerability may help understanding depression. To this aim, on one hand we are using conditional Knock-Out and pharmacogenetic approaches (DREADDs) to study the link between microglial activation, Htr2b, and behavioral changes, and on the other hand, we plan to specify, at the single cell level, the heterogeneity and plasticity of microglia/neuron interaction. Techniques used are cell biology, imaging, neuropharmacology, molecular biology and behavioral experiments.

Address: Institut du Fer à Moulin - 17, rue du Fer à Moulin 75005 PARIS

Phone number: +33 1 45 87 61 24 ;

Email: anne.roumier@inserm.fr

Website

Superviseur: 

Anne ROUMIER & Luc MAROTEAUX