Dr DARCQ Emmanuel

Super-potent opioids could be safer-than-expected alternatives to conventional painkillers.

Mathis V, Darcq E

Nature. 2026 04 1;:

IFNγ-associated immune-metabolic remodeling is linked to serotonin-kynurenine imbalance and cortical vulnerability in lupus-prone mice.

Matmat K, Guéant-Rodriguez RM, Darcq E, Baspinar O, Alberto JM, Guéant JL, Mensah-Nyagan AG, Jeltsch-David H

Front Immunol. 2026 03 5;17:1740039

Incubation of social deficit during morphine abstinence in male mice using a novel unbiased and automatized method.

Mathis VP, Giua G, Torquet N, Mittelhaeuser C, Bour R, Kieffer BL, Riet F, Darcq E

Front Behav Neurosci. 2025 10 29;19:1697469

The neural circuits and signalling pathways of opioid use disorder.

Mathis VP, Ehrlich AT, Darcq E

Nat Rev Neurosci. 2025 10 27;:

The GPR88 Agonist RTI-122 Reduces Alcohol-Related Motivation and Consumption.

Lovelock DF, Liu W, Hamida SB, Cordero VL, Van Voorhies KJ, Martin M, Olmo IG, Darcq E, Rahman MT, Naassila M, Kieffer BL, Jin C, Besheer J

Addict Biol. 2025 ;30(6):e70058

Discovery of BI-9508, a Brain-Penetrant GPR88-Receptor-Agonist Tool Compound for Mouse Studies.

Fer M, Amalric C, Arban R, Baron L, Ben Hamida S, Breh-Schlanser P, Cui Y, Darcq E, Eickmeier C, Faye V, Franchet C, Frauli M, Halter C, Heyer M, Hoenke C, Hoerer S, Hucke OT, Joseph C, Kieffer BL, Lebrun L, Lotz N, Mayer S, Omrani A, Recolet M, Schaeffer L, Schann S, Schlecker A, Steinberg E, Viloria M, Würstle K, Young K, Zinser A, Montel F, Klepp J

J Med Chem. 2024 07 1;:

Model of negative affect induced by withdrawal from acute and chronic morphine administration in male mice.

Ozdemir D, Meyer J, Kieffer BL, Darcq E

Sci Rep. 2024 04 29;14(1):9767

Neuroscience and addiction research: current advances and perspectives.

Darcq E, Kieffer BL

J Neural Transm (Vienna). 2024 03 16;:

Chronic morphine leaves a durable fingerprint on whole brain functional connectivity.

Sourty M, Champagnol-Di Liberti C, Nasseef MT, Welsch L, Noblet V, Darcq E, Kieffer BL

Biol Psychiatry. 2023 12 15;:

Mu Opioid Receptor-Expressing Neurons in the Dorsal Raphe Nucleus Are Involved in Reward Processing and Affective Behaviors.

Welsch L, Colantonio E, Frison M, Johnson DA, McClain SP, Mathis V, Banghart MR, Ben Hamida S, Darcq E, Kieffer BL

Biol Psychiatry. 2023 12 1;94(11):842-851

Manipulating ΔFOSB in D1-type Medium Spiny Neurons of the nucleus accumbens reshapes whole brain functional connectivity.

Sourty M, Nasseef MT, Champagnol-Di Liberti C, Mondino M, Noblet V, Parise EM, Markovic T, Browne CJ, Darcq E, Nestler EJ, Kieffer BL

Biol Psychiatry. 2023 07 28;:

Advances in the characterization of negative affect caused by acute and protracted opioid withdrawal using animal models.

Ozdemir D, Allain F, Kieffer BL, Darcq E

Neuropharmacology. 2023 07 1;232:109524

Mu opioid receptor-positive neurons in the dorsal raphe nucleus are impaired by morphine abstinence.

Welsch L, Colantonio E, Falconnier C, Champagnol-DiLiberti C, Allain F, Ben Hamida S, Darcq E, Lutz PE, Kieffer BL

Biol Psychiatry. 2023 06 29;:

Habenular Neurons Expressing Mu Opioid Receptors Promote Negative Affect in a Projection-Specific Manner.

Bailly J, Allain F, Schwartz E, Tirel C, Dupuy C, Petit F, Diana MA, Darcq E, Kieffer BL

Biol Psychiatry. 2023 06 15;93(12):1108-1117

Chronic tianeptine induces tolerance in analgesia and hyperlocomotion via mu-opioid receptor activation in mice.

Allain F, Ehrlich AT, McNicholas M, Gross F, Ma W, Kieffer BL, Darcq E

Front Psychiatry. 2023 05 23;14:1186397

Reduced dopamine release in Dcc haploinsufficiency male mice abolishes the rewarding effects of cocaine but not those of morphine and ethanol.

Darcq E, Nouel D, Hernandez G, Pokinko M, Ash P, Moquin L, Gratton A, Kieffer B, Flores C

Psychopharmacology (Berl). 2023 03;240(3):637-646

Striatal μ-opioid receptor activation triggers direct-pathway GABAergic plasticity and induces negative affect.

Wang W, Xie X, Zhuang X, Huang Y, Tan T, Gangal H, Huang Z, Purvines W, Wang X, Stefanov A, Chen R, Rodriggs L, Chaiprasert A, Yu E, Vierkant V, Hook M, Huang Y, Darcq E, Wang J

Cell Rep. 2023 02 28;42(2):112089

Improvement of the Metabolic Stability of GPR88 Agonist RTI-13951-33: Design, Synthesis, and Biological Evaluation.

Rahman MT, Decker AM, Ben Hamida S, Perrey DA, Chaminda Lakmal HH, Maitra R, Darcq E, Kieffer BL, Jin C

J Med Chem. 2023 02 23;66(4):2964-2978

Synthesis and pharmacological validation of a novel radioligand for the orphan GPR88 receptor.

Decker AM, Rahman MT, Kormos CM, Hesk D, Darcq E, Kieffer BL, Jin C

Bioorg Med Chem Lett. 2023 01 15;80:129120

The mu opioid receptor and the orphan receptor GPR151 contribute to social reward in the habenula.

Allain F, Carter M, Dumas S, Darcq E, Kieffer BL

Sci Rep. 2022 11 24;12(1):20234

Supraspinal melatonin MT receptor agonism alleviates pain via a neural circuit that recruits mu opioid receptors.

Posa L, De Gregorio D, Lopez-Canul M, He Q, Darcq E, Rullo L, Pearl-Dowler L, Luongo L, Candeletti S, Romualdi P, Kieffer BL, Gobbi G

J Pineal Res. 2022 11;73(4):e12825

The GPR88 agonist RTI-13951-33 reduces alcohol drinking and seeking in mice.

Ben Hamida S, Carter M, Darcq E, Sourty M, Rahman MT, Decker AM, Jin C, Kieffer BL

Addict Biol. 2022 11;27(6):e13227

The orphan receptor GPR88 controls impulsivity and is a risk factor for Attention-Deficit/Hyperactivity Disorder.

Ben Hamida S, Sengupta SM, Clarke E, McNicholas M, Moroncini E, Darcq E, Ter-Stepanian M, Fortier MÈ, Grizenko N, Joober R, Kieffer BL

Mol Psychiatry. 2022 11;27(11):4662-4672

Chronic generalized pain disrupts whole brain functional connectivity in mice.

Nasseef MT, Ma W, Singh JP, Dozono N, Lançon K, Séguéla P, Darcq E, Ueda H, Kieffer BL

Brain Imaging Behav. 2021 10;15(5):2406-2416

Ackr3-Venus knock-in mouse lights up brain vasculature.

Ehrlich AT, Semache M, Couvineau P, Wojcik S, Kobayashi H, Thelen M, Gross F, Hogue M, Le Gouill C, Darcq E, Bouvier M, Kieffer BL

Mol Brain. 2021 09 28;14(1):151

Evaluation of Amide Bioisosteres Leading to 1,2,3-Triazole Containing Compounds as GPR88 Agonists: Design, Synthesis, and Structure-Activity Relationship Studies.

Rahman MT, Decker AM, Laudermilk L, Maitra R, Ma W, Ben Hamida S, Darcq E, Kieffer BL, Jin C

J Med Chem. 2021 08 26;64(16):12397-12413

Recent advances in basic science methodology to evaluate opioid safety profiles and to understand opioid activities.

Ehrlich AT, Darcq E

Fac Rev. 2021 02 19;10:15

Design, Synthesis, and Structure-Activity Relationship Studies of (4-Alkoxyphenyl)glycinamides and Bioisosteric 1,3,4-Oxadiazoles as GPR88 Agonists.

Rahman MT, Decker AM, Langston TL, Mathews KM, Laudermilk L, Maitra R, Ma W, Darcq E, Kieffer BL, Jin C

J Med Chem. 2020 12 10;63(23):14989-15012

Targeting Morphine-Responsive Neurons: Generation of a Knock-In Mouse Line Expressing Cre Recombinase from the Mu-Opioid Receptor Gene Locus.

Bailly J, Del Rossi N, Runtz L, Li JJ, Park D, Scherrer G, Tanti A, Birling MC, Darcq E, Kieffer BL

eNeuro. 2020 05 29;7(3):

GPCR and Alcohol-Related Behaviors in Genetically Modified Mice.

Neasta J, Darcq E, Jeanblanc J, Carnicella S, Ben Hamida S

Neurotherapeutics. 2020 01;17(1):17-42

Mu opioid receptors in the medial habenula contribute to naloxone aversion.

Boulos LJ, Ben Hamida S, Bailly J, Maitra M, Ehrlich AT, Gavériaux-Ruff C, Darcq E, Kieffer BL

Neuropsychopharmacology. 2020 01;45(2):247-255

The Negative Affect of Protracted Opioid Abstinence: Progress and Perspectives From Rodent Models.

Welsch L, Bailly J, Darcq E, Kieffer BL

Biol Psychiatry. 2020 01 1;87(1):54-63

Control of aversion by glycine-gated GluN1/GluN3A NMDA receptors in the adult medial habenula.

Otsu Y, Darcq E, Pietrajtis K, Mátyás F, Schwartz E, Bessaih T, Abi Gerges S, Rousseau CV, Grand T, Dieudonné S, Paoletti P, Acsády L, Agulhon C, Kieffer BL, Diana MA

Science. 2019 10 11;366(6462):250-254

Oxycodone-Mediated Activation of the Mu Opioid Receptor Reduces Whole Brain Functional Connectivity in Mice.

Nasseef MT, Singh JP, Ehrlich AT, McNicholas M, Park DW, Ma W, Kulkarni P, Kieffer BL, Darcq E

ACS Pharmacol Transl Sci. 2019 08 9;2(4):264-274

GPR88 in D1R-Type and D2R-Type Medium Spiny Neurons Differentially Regulates Affective and Motor Behavior.

Meirsman AC, Ben Hamida S, Clarke E, de Kerchove d'Exaerde A, Darcq E, Kieffer BL

eNeuro. 2019 08 8;6(4):

Biased Signaling of the Mu Opioid Receptor Revealed in Native Neurons.

Ehrlich AT, Semache M, Gross F, Da Fonte DF, Runtz L, Colley C, Mezni A, Le Gouill C, Lukasheva V, Hogue M, Darcq E, Bouvier M, Kieffer BL

iScience. 2019 04 26;14:47-57

Current strategies toward safer mu opioid receptor drugs for pain management.

Ehrlich AT, Kieffer BL, Darcq E

Expert Opin Ther Targets. 2019 04;23(4):315-326

TouchScreen-based phenotyping: altered stimulus/reward association and lower perseveration to gain a reward in mu opioid receptor knockout mice.

Boulos LJ, Nasseef MT, McNicholas M, Mechling A, Harsan LA, Darcq E, Ben Hamida S, Kieffer BL

Sci Rep. 2019 03 11;9(1):4044

Recommending buprenorphine for pain management.

Ehrlich AT, Darcq E

Pain Manag. 2019 01 1;9(1):13-16

Deformation-based Morphometry MRI Reveals Brain Structural Modifications in Living Mu Opioid Receptor Knockout Mice.

Nasseef MT, Devenyi GA, Mechling AE, Harsan LA, Chakravarty MM, Kieffer BL, Darcq E

Front Psychiatry. 2018 12 3;9:643

Lack of anticipatory behavior in Gpr88 knockout mice showed by automatized home cage phenotyping.

Maroteaux G, Arefin TM, Harsan LA, Darcq E, Ben Hamida S, Kieffer BL

Genes Brain Behav. 2018 11;17(8):e12473

Rare susceptibility variants for bipolar disorder suggest a role for G protein-coupled receptors.

Cruceanu C, Schmouth JF, Torres-Platas SG, Lopez JP, Ambalavanan A, Darcq E, Gross F, Breton B, Spiegelman D, Rochefort D, Hince P, Petite JM, Gauthier J, Lafrenière RG, Dion PA, Greenwood CM, Kieffer BL, Alda M, Turecki G, Rouleau GA

Mol Psychiatry. 2018 10;23(10):2050-2056

Discovery of a Potent, Selective, and Brain-Penetrant Small Molecule that Activates the Orphan Receptor GPR88 and Reduces Alcohol Intake.

Jin C, Decker AM, Makhijani VH, Besheer J, Darcq E, Kieffer BL, Maitra R

J Med Chem. 2018 08 9;61(15):6748-6758

Expression map of 78 brain-expressed mouse orphan GPCRs provides a translational resource for neuropsychiatric research.

Ehrlich AT, Maroteaux G, Robe A, Venteo L, Nasseef MT, van Kempen LC, Mechawar N, Turecki G, Darcq E, Kieffer BL

Commun Biol. 2018 08 6;1:102

Increased Alcohol Seeking in Mice Lacking Gpr88 Involves Dysfunctional Mesocorticolimbic Networks.

Ben Hamida S, Mendonça-Netto S, Arefin TM, Nasseef MT, Boulos LJ, McNicholas M, Ehrlich AT, Clarke E, Moquin L, Gratton A, Darcq E, Harsan LA, Maldonado R, Kieffer BL

Biol Psychiatry. 2018 08 1;84(3):202-212

Opioid receptors: drivers to addiction?

Darcq E, Kieffer BL

Nat Rev Neurosci. 2018 08;19(8):499-514

Mapping GPR88-Venus illuminates a novel role for GPR88 in sensory processing.

Ehrlich AT, Semache M, Bailly J, Wojcik S, Arefin TM, Colley C, Le Gouill C, Gross F, Lukasheva V, Hogue M, Darcq E, Harsan LA, Bouvier M, Kieffer BL

Brain Struct Funct. 2018 04;223(3):1275-1296

Fyn Signaling Is Compartmentalized to Dopamine D1 Receptor Expressing Neurons in the Dorsal Medial Striatum.

Phamluong K, Darcq E, Wu S, Sakhai SA, Ron D

Front Mol Neurosci. 2017 08 31;10:273

Mu Opioid Receptors in Gamma-Aminobutyric Acidergic Forebrain Neurons Moderate Motivation for Heroin and Palatable Food.

Charbogne P, Gardon O, Martín-García E, Keyworth HL, Matsui A, Mechling AE, Bienert T, Nasseef MT, Robé A, Moquin L, Darcq E, Ben Hamida S, Robledo P, Matifas A, Befort K, Gavériaux-Ruff C, Harsan LA, von Elverfeldt D, Hennig J, Gratton A, Kitchen I, Bailey A, Alvarez VA, Maldonado R, Kieffer BL

Biol Psychiatry. 2017 05 1;81(9):778-788

Translating the Habenula-From Rodents to Humans.

Boulos LJ, Darcq E, Kieffer BL

Biol Psychiatry. 2017 02 15;81(4):296-305

BOLD Imaging in Awake Wild-Type and Mu-Opioid Receptor Knock-Out Mice Reveals On-Target Activation Maps in Response to Oxycodone.

Moore K, Madularu D, Iriah S, Yee JR, Kulkarni P, Darcq E, Kieffer BL, Ferris CF

Front Neurosci. 2016 11 3;10:471

Deletion of the mu opioid receptor gene in mice reshapes the reward-aversion connectome.

Mechling AE, Arefin T, Lee HL, Bienert T, Reisert M, Ben Hamida S, Darcq E, Ehrlich A, Gaveriaux-Ruff C, Parent MJ, Rosa-Neto P, Hennig J, von Elverfeldt D, Kieffer BL, Harsan LA

Proc Natl Acad Sci U S A. 2016 10 11;113(41):11603-11608

The Neurotrophic Factor Receptor p75 in the Rat Dorsolateral Striatum Drives Excessive Alcohol Drinking.

Darcq E, Morisot N, Phamluong K, Warnault V, Jeanblanc J, Longo FM, Massa SM, Ron D

J Neurosci. 2016 09 28;36(39):10116-27

The BDNF Valine 68 to Methionine Polymorphism Increases Compulsive Alcohol Drinking in Mice That Is Reversed by Tropomyosin Receptor Kinase B Activation.

Warnault V, Darcq E, Morisot N, Phamluong K, Wilbrecht L, Massa SM, Longo FM, Ron D

Biol Psychiatry. 2016 03 15;79(6):463-73

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