Evidence map›Paper›PMID 27469513›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2016

Effects of Ketamine and Ketamine Metabolites on Evoked Striatal Dopamine Release, Dopamine Receptors, and Monoamine Transporters.

Adem Can, Panos Zanos, Ruin Moaddel, Hye Jin Kang, Katinia S S Dossou, Irving W Wainer, Joseph F Cheer, Douglas O Frost, Xi-Ping Huang, Todd D Gould

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
12.9field-weighted citation impact, top 1% 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

58 citing papers in PubMed, 111 citations in OpenAlex.

  1. Ketamine metabolites, clinical response, and gamma power in a randomized, placebo-controlled, crossover trial for treatment-resistant major depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020
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  7. ThePhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024
    Review
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  12. Microdosing ketamine inbioRxiv : the preprint server for biology · 2023
    Article
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  14. Review
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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

10 authors at 1 institution in 1 country.

Adem CanDepartment of Psychiatry (A.C., P.Z., J.F.C., D.O.F., T.D.G.), Department of Pharmacology (D.O.F, T.D.G), and Department of Anatomy and Neurobiology (J.F.C, T.D.G), University of Maryland School of Medicine, Baltimore, Maryland; Department of Psychology, Notre Dame of Maryland University, Baltimore, Maryland (A.C.); Biomedical Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland (R.M., K.S.S.D., I.W.W.); National Institute of Mental Health Psychoactive Drug Screening Program, Department of Pharmacology, University of North Carolina Chapel Hill Medical School, Chapel Hill, North Carolina (H.J.K., X.-P.H.); and Mitchell Woods Pharmaceuticals, Shelton, Connecticut (I.W.W.).
Panos ZanosDepartment of Psychiatry (A.C., P.Z., J.F.C., D.O.F., T.D.G.), Department of Pharmacology (D.O.F, T.D.G), and Department of Anatomy and Neurobiology (J.F.C, T.D.G), University of Maryland School of Medicine, Baltimore, Maryland; Department of Psychology, Notre Dame of Maryland University, Baltimore, Maryland (A.C.); Biomedical Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland (R.M., K.S.S.D., I.W.W.); National Institute of Mental Health Psychoactive Drug Screening Program, Department of Pharmacology, University of North Carolina Chapel Hill Medical School, Chapel Hill, North Carolina (H.J.K., X.-P.H.); and Mitchell Woods Pharmaceuticals, Shelton, Connecticut (I.W.W.).ORCID 0000-0002-1968-8648
Ruin MoaddelDepartment of Psychiatry (A.C., P.Z., J.F.C., D.O.F., T.D.G.), Department of Pharmacology (D.O.F, T.D.G), and Department of Anatomy and Neurobiology (J.F.C, T.D.G), University of Maryland School of Medicine, Baltimore, Maryland; Department of Psychology, Notre Dame of Maryland University, Baltimore, Maryland (A.C.); Biomedical Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland (R.M., K.S.S.D., I.W.W.); National Institute of Mental Health Psychoactive Drug Screening Program, Department of Pharmacology, University of North Carolina Chapel Hill Medical School, Chapel Hill, North Carolina (H.J.K., X.-P.H.); and Mitchell Woods Pharmaceuticals, Shelton, Connecticut (I.W.W.).ORCID 0000-0002-6812-0127
Hye Jin KangDepartment of Psychiatry (A.C., P.Z., J.F.C., D.O.F., T.D.G.), Department of Pharmacology (D.O.F, T.D.G), and Department of Anatomy and Neurobiology (J.F.C, T.D.G), University of Maryland School of Medicine, Baltimore, Maryland; Department of Psychology, Notre Dame of Maryland University, Baltimore, Maryland (A.C.); Biomedical Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland (R.M., K.S.S.D., I.W.W.); National Institute of Mental Health Psychoactive Drug Screening Program, Department of Pharmacology, University of North Carolina Chapel Hill Medical School, Chapel Hill, North Carolina (H.J.K., X.-P.H.); and Mitchell Woods Pharmaceuticals, Shelton, Connecticut (I.W.W.).
Katinia S S DossouDepartment of Psychiatry (A.C., P.Z., J.F.C., D.O.F., T.D.G.), Department of Pharmacology (D.O.F, T.D.G), and Department of Anatomy and Neurobiology (J.F.C, T.D.G), University of Maryland School of Medicine, Baltimore, Maryland; Department of Psychology, Notre Dame of Maryland University, Baltimore, Maryland (A.C.); Biomedical Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland (R.M., K.S.S.D., I.W.W.); National Institute of Mental Health Psychoactive Drug Screening Program, Department of Pharmacology, University of North Carolina Chapel Hill Medical School, Chapel Hill, North Carolina (H.J.K., X.-P.H.); and Mitchell Woods Pharmaceuticals, Shelton, Connecticut (I.W.W.).
Irving W WainerDepartment of Psychiatry (A.C., P.Z., J.F.C., D.O.F., T.D.G.), Department of Pharmacology (D.O.F, T.D.G), and Department of Anatomy and Neurobiology (J.F.C, T.D.G), University of Maryland School of Medicine, Baltimore, Maryland; Department of Psychology, Notre Dame of Maryland University, Baltimore, Maryland (A.C.); Biomedical Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland (R.M., K.S.S.D., I.W.W.); National Institute of Mental Health Psychoactive Drug Screening Program, Department of Pharmacology, University of North Carolina Chapel Hill Medical School, Chapel Hill, North Carolina (H.J.K., X.-P.H.); and Mitchell Woods Pharmaceuticals, Shelton, Connecticut (I.W.W.).
Joseph F CheerDepartment of Psychiatry (A.C., P.Z., J.F.C., D.O.F., T.D.G.), Department of Pharmacology (D.O.F, T.D.G), and Department of Anatomy and Neurobiology (J.F.C, T.D.G), University of Maryland School of Medicine, Baltimore, Maryland; Department of Psychology, Notre Dame of Maryland University, Baltimore, Maryland (A.C.); Biomedical Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland (R.M., K.S.S.D., I.W.W.); National Institute of Mental Health Psychoactive Drug Screening Program, Department of Pharmacology, University of North Carolina Chapel Hill Medical School, Chapel Hill, North Carolina (H.J.K., X.-P.H.); and Mitchell Woods Pharmaceuticals, Shelton, Connecticut (I.W.W.).
Douglas O FrostDepartment of Psychiatry (A.C., P.Z., J.F.C., D.O.F., T.D.G.), Department of Pharmacology (D.O.F, T.D.G), and Department of Anatomy and Neurobiology (J.F.C, T.D.G), University of Maryland School of Medicine, Baltimore, Maryland; Department of Psychology, Notre Dame of Maryland University, Baltimore, Maryland (A.C.); Biomedical Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland (R.M., K.S.S.D., I.W.W.); National Institute of Mental Health Psychoactive Drug Screening Program, Department of Pharmacology, University of North Carolina Chapel Hill Medical School, Chapel Hill, North Carolina (H.J.K., X.-P.H.); and Mitchell Woods Pharmaceuticals, Shelton, Connecticut (I.W.W.).
Xi-Ping HuangDepartment of Psychiatry (A.C., P.Z., J.F.C., D.O.F., T.D.G.), Department of Pharmacology (D.O.F, T.D.G), and Department of Anatomy and Neurobiology (J.F.C, T.D.G), University of Maryland School of Medicine, Baltimore, Maryland; Department of Psychology, Notre Dame of Maryland University, Baltimore, Maryland (A.C.); Biomedical Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland (R.M., K.S.S.D., I.W.W.); National Institute of Mental Health Psychoactive Drug Screening Program, Department of Pharmacology, University of North Carolina Chapel Hill Medical School, Chapel Hill, North Carolina (H.J.K., X.-P.H.); and Mitchell Woods Pharmaceuticals, Shelton, Connecticut (I.W.W.).
Todd D GouldDepartment of Psychiatry (A.C., P.Z., J.F.C., D.O.F., T.D.G.), Department of Pharmacology (D.O.F, T.D.G), and Department of Anatomy and Neurobiology (J.F.C, T.D.G), University of Maryland School of Medicine, Baltimore, Maryland; Department of Psychology, Notre Dame of Maryland University, Baltimore, Maryland (A.C.); Biomedical Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland (R.M., K.S.S.D., I.W.W.); National Institute of Mental Health Psychoactive Drug Screening Program, Department of Pharmacology, University of North Carolina Chapel Hill Medical School, Chapel Hill, North Carolina (H.J.K., X.-P.H.); and Mitchell Woods Pharmaceuticals, Shelton, Connecticut (I.W.W.) gouldlab@me.com.
University of North Carolina at Chapel Hill · US

Funding

Disease Status Drug Metabolism and New Drug Discovery ZIAAG000297 · NIA · NATIONAL INSTITUTE ON AGING · PI EGAN, JOSEPHINE · 2009 to 2025
$38.2M
Therapeutic Efficacy of Ketamine Metabolites for Depression TreatmentR01MH107615 · NIMH · UNIVERSITY OF MARYLAND BALTIMORE · PI GOULD, TODD D · 2016 to 2025
$7.2M
Endogenous Cannabinoid Control of Reward SubstratesR01DA022340 · NIDA · UNIVERSITY OF MARYLAND BALTIMORE · PI Joseph F Cheer · 2008 to 2026
$5.6M
Enduring Consequences of Adolescent Cannabinoid and Methylphenidate ExposureR01DA042595 · NIDA · UNIVERSITY OF MARYLAND BALTIMORE · PI CHEER, JOSEPH F · 2016 to 2020
$2.0M
NIDA NIH HHS R01 DA022340NIDA NIH HHS R01 DA042595NIMH NIH HHS R01 MH107615
6 · The paper itself

Abstract

Following administration at subanesthetic doses, (R,S)-ketamine (ketamine) induces rapid and robust relief from symptoms of depression in treatment-refractory depressed patients. Previous studies suggest that ketamine's antidepressant properties involve enhancement of dopamine (DA) neurotransmission. Ketamine is rapidly metabolized to (2S,6S)- and (2R,6R)-hydroxynorketamine (HNK), which have antidepressant actions independent of N-methyl-d-aspartate glutamate receptor inhibition. These antidepressant actions of (2S,6S;2R,6R)-HNK, or other metabolites, as well as ketamine's side effects, including abuse potential, may be related to direct effects on components of the dopaminergic (DAergic) system. Here, brain and blood distribution/clearance and pharmacodynamic analyses at DA receptors (D1-D5) and the DA, norepinephrine, and serotonin transporters were assessed for ketamine and its major metabolites (norketamine, dehydronorketamine, and HNKs). Additionally, we measured electrically evoked mesolimbic DA release and decay using fast-scan cyclic voltammetry following acute administration of subanesthetic doses of ketamine (2, 10, and 50 mg/kg, i.p.). Following ketamine injection, ketamine, norketamine, and multiple hydroxynorketamines were detected in the plasma and brain of mice. Dehydronorketamine was detectable in plasma, but concentrations were below detectable limits in the brain. Ketamine did not alter the magnitude or kinetics of evoked DA release in the nucleus accumbens in anesthetized mice. Neither ketamine's enantiomers nor its metabolites had affinity for DA receptors or the DA, noradrenaline, and serotonin transporters (up to 10 μM). These results suggest that neither the side effects nor antidepressant actions of ketamine or ketamine metabolites are associated with direct effects on mesolimbic DAergic neurotransmission. Previously observed in vivo changes in DAergic neurotransmission following ketamine administration are likely indirect.

Indexed as

AnimalsDopamineKetamineKineticsMaleMiceMice, Inbred C57BLNeostriatumNorepinephrine Plasma Membrane Transport ProteinsReceptors, DopamineSerotonin Plasma Membrane Transport ProteinsDopamineKetamineNorepinephrine Plasma Membrane Transport ProteinsReceptors, DopamineSerotonin Plasma Membrane Transport Proteins

Identifiers

PMID27469513
PMCPMC5034706
OpenAlexW2484912492

What OpenQuestion holds

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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.