Evidence map›Paper›PMID 26019014›Full record

ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2016

Behavioral and Physiological Effects of a Novel Kappa-Opioid Receptor-Based DREADD in Rats.

Nathan J Marchant, Leslie R Whitaker, Jennifer M Bossert, Brandon K Harvey, Bruce T Hope, Konstantin Kaganovsky, Sweta Adhikary, Thomas E Prisinzano, Eyal Vardy, Bryan L Roth and 1 more

Open access · bronzeAbstract readValidation Study
In one paragraph

Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
4.7field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

46 citing papers in PubMed, 61 citations in OpenAlex.

  1. 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 · 2026
    Review
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  9. Chemogenetics as a neuromodulatory approach to treating neuropsychiatric diseases and disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Review
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  15. Review
  16. Article
  17. The Mesolimbic Dopamine Activity Signatures of Relapse to Alcohol-Seeking.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020
    Article
  18. Review
  19. Chemogenetic Inhibition Reveals That Processing Relative But Not Absolute Threat Requires Basal Amygdala.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 2 countries.

Nathan J MarchantBehavioral Neuroscience Research Branch, IRP-NIDA, NIH, Bethesda, MD, USA.
Leslie R WhitakerBehavioral Neuroscience Research Branch, IRP-NIDA, NIH, Bethesda, MD, USA.
Jennifer M BossertBehavioral Neuroscience Research Branch, IRP-NIDA, NIH, Bethesda, MD, USA.
Brandon K HarveyOptogenetics and Transgenic Technology Core, IRP-NIDA, NIH, Bethesda, MD, USA.
Bruce T HopeBehavioral Neuroscience Research Branch, IRP-NIDA, NIH, Bethesda, MD, USA.
Konstantin KaganovskyBehavioral Neuroscience Research Branch, IRP-NIDA, NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-1577-109X
Sweta AdhikaryBehavioral Neuroscience Research Branch, IRP-NIDA, NIH, Bethesda, MD, USA.
Thomas E PrisinzanoDepartment of Medicinal Chemistry, School of Pharmacy, University of Kansas, Lawrence, KS, USA.
Eyal VardyMerck Research Laboratories, Kenilworth, NJ, USA.
Bryan L RothDepartment of Pharmacology, School of Medicine, University of North Carolina Chapel Hill, Chapel Hill, NC, USA.
Yavin ShahamBehavioral Neuroscience Research Branch, IRP-NIDA, NIH, Bethesda, MD, USA.
University of North Carolina at Chapel Hill · USThe University of Melbourne · AUUniversity of Kansas · US

Funding

Neurobiology Of Relapse To Opiate and Psychostimulant DrugsZIADA000434 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI SHAHAM, YAVIN · 2009 to 2025
$39.8M
Characterization of neuronal ensembles activated during drug-induced behaviorZIADA000467 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI HOPE, BRUCE · 2009 to 2025
$35.8M
Optogenetics and Transgenic Technology CoreZICDA000555 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI HARVEY, BRANDON · 2009 to 2017
$10.0M
Investigation of Neoclerodanes as Novel Opioid LigandsR01DA018151 · NIDA · UNIVERSITY OF KENTUCKY · PI PRISINZANO, THOMAS EDWARD · 2005 to 2020
$5.7M
Gene Delivery and AddictionZIADA000526 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI HARVEY, BRANDON · 2009 to 2022
$3.2M
DREADD2.0: AN ENHANCED CHEMOGENETIC TOOLKITU01MH105892 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JIN, JIAN, KASH, THOMAS L. · 2014 to 2016
$3.0M
Gene Therapy And NeurodegenerationZIADA000443 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI HARVEY, BRANDON · 2009 to 2020
$2.7M
Intramural NIH HHS Z99 DA999999NIDA NIH HHS DA018151NIDA NIH HHS R01 DA018151NIMH NIH HHS U01 MH105892
6 · The paper itself

Abstract

In the past decade, novel methods using engineered receptors have enabled researchers to manipulate neuronal activity with increased spatial and temporal specificity. One widely used chemogenetic method in mice and rats is the DREADD (designer receptors exclusively activated by designer drugs) system in which a mutated muscarinic G protein-coupled receptor is activated by an otherwise inert synthetic ligand, clozapine-N-oxide (CNO). Recently, the Roth laboratory developed a novel inhibitory DREADD in which a mutated kappa-opioid receptor (KORD) is activated by the pharmacologically inert drug salvinorin B (SalB; Vardy et al, 2015). They demonstrated the feasibility of using KORD to study brain circuits involved in motivated behavior in mice. Here, we used behavioral, electrophysiological, and neuroanatomical methods to demonstrate the feasibility of using the novel KORD to study brain circuits involved in motivated behavior in rats. In Exp. 1, we show that SalB dose-dependently decreased spontaneous and cocaine-induced locomotor activity in rats expressing KORD to midbrain (ventral tegmental area/substantia nigra). In Exp. 2, we show that SalB completely inhibited tonic firing in KORD-expressing putative dopamine neurons in midbrain. In Exp. 3, we used a 'retro-DREADD' dual-virus approach to restrict expression of KORD in ventral subiculum neurons that project to nucleus accumbens shell. We show that KORD activation selectively decreased novel context-induced Fos expression in this projection. Our results indicate that the novel KORD is a promising tool to selectively inactivate brain areas and neural circuits in rat studies of motivated behavior.

Indexed as

Gene Transfer TechniquesAction PotentialsAnimalsCentral Nervous System AgentsCocaineDependovirusDiterpenesDiterpenes, ClerodaneDopamine Uptake InhibitorsFeasibility StudiesGenetic EngineeringGenetic VectorsMaleMesencephalonMotor ActivityMutationCentral Nervous System AgentsCocaineDiterpenesDiterpenes, ClerodaneDopamine Uptake InhibitorsReceptors, Opioid, kappasalvinorin B

Identifiers

PMID26019014
PMCPMC5130116
OpenAlexW2254490564

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.