ArticleNeuron2015
A New DREADD Facilitates the Multiplexed Chemogenetic Interrogation of Behavior.
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Article in Neuron, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 233 papers.
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233citing papers in PubMed
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Who cites it
233 citing papers in PubMed.
- Article
- Overview of the DREADDs chemogenetics and the patent landscape of their actuators.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Light-activated tetanus neurotoxin for conditional proteolysis and inducible synaptic inhibition in vivo.Nature methods · 2026Article
- Functional remodeling of the parasubthalamic nucleus drives alcohol drinking escalation in dependence.bioRxiv : the preprint server for biology · 2026Article
- Functional interrogation of neuronal connections by chemoptogenetic presynaptic ablation.Science advances · 2026Article
- High-throughput assessment of vocal modulation following chemogenetic inhibition in songbirds.iScience · 2026Article
- Redirecting engineered immune cells using G protein-coupled receptors in cancer therapy.Immuno-oncology technology · 2026Review
- Disrupted temperature-sleep coupling mechanism in a Dravet syndrome mouse model.Nature communications · 2026Article
- Devaluation of response-produced safety signals reveals circuits for goal-directed versus habitual avoidance in dorsal striatum.Nature communications · 2026Article
- Interrogating Physiological Functions with Light and Chemicals.Annual review of physiology · 2026Review
- A chemogenetic approach for temporal and cell-specific activation of endogenous GPCRs in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Genetic manipulation technologies for precise cellular control: a comparative review of five approaches.Frontiers in bioengineering and biotechnology · 2026Review
- Advances in chemogenetics: a review of DREADDs and its application in psychiatric disorders.Molecular psychiatry · 2026Review
- Voltage-Gated and Chemogenetic Modulation of Calcium Signaling in Oligodendrocyte Development and Synaptic Integration.Journal of neurochemistry · 2025Review
- Reducing ventral hippocampal CA1/subiculum hyperexcitability restores social memory and alleviates anxiety-related behavior in a mouse model of temporal lobe epilepsy.bioRxiv : the preprint server for biology · 2025Article
- The Future of Chemogenetics for the Treatment of Spasticity.Molecular diagnosis & therapy · 2025Review
- Nucleus accumbens core chemogenetic excitation in male mice and chemogenetic inhibition in female mice reduced ethanol reward.Biology of sex differences · 2025Article
- Genetics-Based Targeting Strategies for Precise Neuromodulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Article
- Sex-dependent modulation of behavioral allocation via ventral tegmental area-nucleus accumbens shell circuitry.NeuroImmune pharmacology and therapeutics · 2025Article
173 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors.
Eyal VardyDepartment of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program (NIMH PDSP), University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA.
J Elliott RobinsonNeurology Department, University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA; Curriculum in Neurobiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Chia LiDiabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA; National Institute of Drug Abuse, Baltimore, MD 21224, USA.
Reid H J OlsenDepartment of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program (NIMH PDSP), University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA; Curriculum in Neurobiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Jeffrey F DiBertoNeurology Department, University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA.
Patrick M GiguereDepartment of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program (NIMH PDSP), University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA.
Flori M SassanoDepartment of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program (NIMH PDSP), University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA.
Xi-Ping HuangDepartment of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program (NIMH PDSP), University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA.
Hu ZhuDepartment of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program (NIMH PDSP), University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA.
Daniel J UrbanDepartment of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program (NIMH PDSP), University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA.
Kate L WhiteDepartment of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program (NIMH PDSP), University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA.
Joseph E RittinerCurriculum in Neurobiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Nicole A CrowleyDepartment of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program (NIMH PDSP), University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA; Curriculum in Neurobiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Kristen E PleilDepartment of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program (NIMH PDSP), University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA; Curriculum in Neurobiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Christopher M MazzoneDepartment of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program (NIMH PDSP), University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA; Curriculum in Neurobiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Philip D MosierDepartment of Medicinal Chemistry, Virginia Commonwealth University School of Pharmacy, Richmond, VA 23298, USA.
Juan SongDepartment of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program (NIMH PDSP), University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA; Curriculum in Neurobiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Thomas L KashDepartment of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program (NIMH PDSP), University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA; Curriculum in Neurobiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
C J MalangaNeurology Department, University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA; Curriculum in Neurobiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Michael J KrashesDiabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA; National Institute of Drug Abuse, Baltimore, MD 21224, USA. Electronic address: michael.krashes@nih.gov.
Bryan L RothDepartment of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program (NIMH PDSP), University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA; Curriculum in Neurobiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. Electronic address: bryan_roth@med.unc.edu.
Funding
UNC ARC Information/Dissemination CoreP60AA011605 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Thomas L. Kash · 2003 to 2026
$46.3MUNC Neuroscience Center Research Cores: MicroscopyP30NS045892 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ZYLKA, MARK J. · 2003 to 2022
$11.5MStructure-Function of Opioid ReceptorsP01DA035764 · NIDA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHEREZOV, VADIM, KATRITCH, VSEVOLOD · 2014 to 2018
$7.1MPREDOCTORAL TRAINING IN PHARMACOLOGICAL SCIST32GM007040 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI NICHOLAS, ROBERT A · 1985 to 2019
$6.0MProbing Ethanol Induced Acceleration of Hindbrain and Amygdalar Pathology in an Alzheimer’s Disease ModelU01AA020911 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Thomas L. Kash, Zoe Anastasia McElligott · 2012 to 2026
$5.8MThe Role of Serotonin in Alcohol-Withdrawal Induced AnxietyR01AA019454 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Thomas L. Kash · 2010 to 2026
$5.6MUnraveling hippocampal networks related to food memoriesZIADK075089 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI KRASHES, MICHAEL J. · 2013 to 2025
$4.7MProbing neural circuits underlying satietyZIADK075087 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI KRASHES, MICHAEL J. · 2013 to 2025
$4.7MInvestigating the interaction of motivational systemsZIADK075090 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI KRASHES, MICHAEL J. · 2013 to 2025
$4.7MDiterpines as Selective Kappa Opioid Receptor AgonistsR01DA017204 · NIDA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ROTH, BRYAN L. · 2003 to 2014
$3.2MDREADD2.0: AN ENHANCED CHEMOGENETIC TOOLKITU01MH105892 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JIN, JIAN, KASH, THOMAS L. · 2014 to 2016
$3.0MEffects of Acute and Chronic Alcohol on Brain Reward in MiceR01AA018335 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MALANGA, C J · 2010 to 2013
$1.3MIntramural NIH HHSNIAAA NIH HHS F30 AA021312NIAAA NIH HHS F31AA02228001NIAAA NIH HHS P60 AA011605NIAAA NIH HHS R00 AA017668NIAAA NIH HHS R00AA017668NIAAA NIH HHS R01 AA018335NIAAA NIH HHS R01 AA019454NIAAA NIH HHS R01AA019454NIAAA NIH HHS U01 AA020911NIAAA NIH HHS U01AA020911NIDA NIH HHS P01 DA035764NIDA NIH HHS P01DA035764NIDA NIH HHS R01 DA017204NIDDK NIH HHS DK075087NIDDK NIH HHS DK075089NIGMS NIH HHS T32 GM007040NIMH NIH HHS U01 MH105892NIMH NIH HHS UO1MH105892NINDS NIH HHS P30 NS045892
Abstract
DREADDs are chemogenetic tools widely used to remotely control cellular signaling, neuronal activity, and behavior. Here we used a structure-based approach to develop a new Gi-coupled DREADD using the kappa-opioid receptor as a template (KORD) that is activated by the pharmacologically inert ligand salvinorin B (SALB). Activation of virally expressed KORD in several neuronal contexts robustly attenuated neuronal activity and modified behaviors. Additionally, co-expression of the KORD and the Gq-coupled M3-DREADD within the same neuronal population facilitated the sequential and bidirectional remote control of behavior. The availability of DREADDs activated by different ligands provides enhanced opportunities for investigating diverse physiological systems using multiplexed chemogenetic actuators.
Indexed as
AnimalsBehavior, AnimalDiterpenesDiterpenes, ClerodaneLigandsMice, Inbred C57BLNeuronsReceptors, Opioid, kappaSignal TransductionDiterpenesDiterpenes, ClerodaneLigandsReceptors, Opioid, kappasalvinorin B
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