IGBMC Recherche

Team leader : Brigitte KIEFFER

Contact : briki@igbmc.fr
Tel. +33 (0) 3 88 65 56 93

Research interests :

We study the role of opioid receptors in pain control, addictive behaviors and emotional responses. We explore the genetic basis of neuroadaptations to drugs of abuse. We also study the role of N/OFQ neuropeptide in cognitive and emotional processes.
Our laboratory combines in vitro and in vivo mutagenesis with pharmacological approches, cellular imaging and behavior.

Highlight :

We recently have created knockin mice expressing functional fluorescent opioid receptors instead of native receptors: the receptor is directly visible in vivo. The movie shows real-time receptor internalization in live neurons, under opioid stimulation. (Movie)

Team members :

Permanent scientist(s) :
Jérôme BECKER
Katia BEFORT
Claire GAVERIAUX-RUFF
Brigitte KIEFFER
Dominique MASSOTTE
Abdel-Mouttalib OUAGAZZAL
Michel ROUX
Aline STEPHAN

Post-doctoral fellow(s):
Julie LE MERRER
Chihiro NOZAKI TAKAHASHI

Graduate Student(s):
Paul CHU SIN CHUNG
Emmanuel DARCQ
Carolina DEL-BOCA
Lauren FAGET
Olivier GARDON
Pierre-Eric LUTZ
Xavier REZAI
Raphaël WEIBEL

Master Students:

Engineers/Technicians
Eric ERBS
Dominique FILLIOL
Audrey MATIFAS
David REISS
Anne ROBE

Main publications :

Le Merrer, J., Becker,J.A.J., Befort, K., and Kieffer, B.L. (2009)Reward processing by the opioid system in the brain. Physiol Rev. 89: 1379-412.

Olmstead C., Ouaggazzal A-M. and Kieffer B. L. (2009) Mu and delta opioid receptors oppositely regulate motor impulsivity in the signaled nose poke task. PLoS ONE 4 : 2, e4410.
Cited in the Editor’s choice section of Science (2009) 323, 984-985.

Scherrer G, Imamachi N, Cao YQ, Contet C, Mennicken F, O’Donnell D, Kieffer BL and Basbaum AI. (2009) Dissociation of the opioid receptor mechanisms that control mechanical and thermal pain. Cell 137, 1148-59.

Pradhan A., Becker J., Scherrer G., Tryoen-Toth P., Filliol D., Matifas A., Massotte D., Gavériaux-Ruff, C and Kieffer B. L. (2009) In vivo delta opioid receptor internalization controls behavioral responses to agonists. PLoS ONE 4(5) : e5425.

Goeldner, C., Reiss, D., Wichmann, J., Meziane H., Kieffer, B.L., Ouagazzal A.M. (2008) Nociceptin receptor impairs recognition memory via interaction with NMDA receptor-dependent mitogen-activated protein kinase/extracellular signal-regulated kinase signaling in the hippocampus. J.Neurosci. 28(9) : 2190-8.

Befort, K., Filliol, D., Ghate, A., Darcq, E., Matifas, A., Muller, J., Lardenois, A., Thibault, C., Dembele, D., Le Merrer, J., Becker, J.A.J., Poch, O. and Kieffer, B.L. (2008) Mu-opioid receptor activation induces transcriptional plasticity in the central extended amygdala. Eur. J. Neurosci. 27, 2973-2984.

Gavériaux-Ruff, C., Karchewski, L.A., Hever, X., Matifas, A., and Kieffer, B.L. (2008) Inflammatory pain is enhanced in delta opioid receptor-knockout mice. Eur. J. Neurosci. 27, 2558-67.

Gavériaux-Ruff C, Kieffer BL. (2007) Conditional gene targeting in the mouse nervous system: Insights into brain function and diseases. Pharmacol Ther. 113(3):619-34.

Scherrer G., Tryoen-Tóth P., Filliol D., Matifas A., Laustriat D., Cao Y. Q., Basbaum A. I., Dierich D., Vonesh J.-L., Gavériaux-Ruff C. and Kieffer B. L. (2006) Knock-in mice expressing fluorescent delta opioid receptors uncover G protein coupled receptor dynamics in vivo Proc. Natl. Acad. Sci. USA 103, 9691-6.

Contet C. S, Kieffer B. L. and Befort K. (2004) Mu opioid receptor: a gateway to drug addiction. Curr. Op. Neurobiol. 14, 1-9.

Décaillot, F., Befort K., Filliol, D., Yue, S-Y., Walker, P. and Kieffer B. L. (2003) Opioid receptor random mutagenesis reveals a mechanism for G protein coupled receptor activation. Nature Structural Biology 10, 629-636.

Filliol D., Ghozland S., Chluba J., Martin M., Matthes H. W., Simonin F., Befort K., Gavériaux-Ruff C., Dierich A., LeMeur M., Valverde O., Maldonado R. and Kieffer B. L. (2000) Mu- and delta-opioid receptor-deficient mice exhibit opposing alterations of emotional responses. Nature Genetics 25, 195-199.

Matthes, H. W. D., Maldonado, R., Simonin, F., Valverde, O., Slowe, S., Kitchen, I, Befort, K., Dierich, A., Le Meur, M., Dollé, P., Tzavara, E., Hanoune, J., Roques, B. P. and Kieffer, B. L. (1996). Loss of morphine-induced analgesia, reward effect and withdrawal symptoms in mice lacking the mu-opioid receptor gene Nature 383, 819-823.