The effects of ketamine on dopaminergic function: meta-analysis and review of the implications for neuropsychiatric disorders

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Title: The effects of ketamine on dopaminergic function: meta-analysis and review of the implications for neuropsychiatric disorders
Authors: Kokkinou, M
Ashok, AH
Howes, OD
Item Type: Journal Article
Abstract: Ketamine is a non-competitive antagonist at the N-methyl-d-aspartate receptor. It has recently been found to have antidepressant effects and is a drug of abuse, suggesting it may have dopaminergic effects. To examine the effect of ketamine on the dopamine systems, we carried out a systematic review and meta-analysis of dopamine measures in the rodent, human and primate brain following acute and chronic ketamine administration relative to a drug-free baseline or control condition. Systematic search of PubMed and PsychInfo electronic databases yielded 40 original peer-reviewed studies. There were sufficient rodent studies of the acute effects of ketamine at sub-anaesthetic doses for meta-analysis. Acute ketamine administration in rodents is associated with significantly increased dopamine levels in the cortex (Hedge’s g= 1.33, P<0.01), striatum (Hedge’s g=0.57, P<0.05) and the nucleus accumbens (Hedge’s g=1.30, P<0.05) compared to control conditions, and 62–180% increases in dopamine neuron population activity. Sub-analysis indicated elevations were more marked in in vivo (g=1.93) than ex vivo (g=0.50) studies. There were not enough studies for meta-analysis in other brain regions studied (hippocampus, ventral pallidum and cerebellum), or of the effects of chronic ketamine administration, although consistent increases in cortical dopamine levels (from 88 to 180%) were reported in the latter studies. In contrast, no study showed an effect of anaesthetic doses (>100 mg kg−1) of ketamine on dopamine levels ex vivo, although this remains to be tested in vivo. Findings in non-human primates and in human studies using positron emission tomography were not consistent. The studies reviewed here provide evidence that acute ketamine administration leads to dopamine release in the rodent brain. We discuss the inter-species variation in the ketamine induced dopamine release as well as the implications for understanding psychiatric disorders, in particular substance abuse, schizophrenia, and the potential antidepressant properties of ketamine, and comparisons with stimulants and other NMDA antagonists. Finally we identify future research needs.
Issue Date: 3-Oct-2017
Date of Acceptance: 17-Jul-2017
URI: http://hdl.handle.net/10044/1/50146
DOI: https://dx.doi.org/10.1038/mp.2017.190
ISSN: 1476-5578
Publisher: Nature Publishing Group
Start Page: 59
End Page: 69
Journal / Book Title: Molecular Psychiatry
Volume: 23
Copyright Statement: © The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/ by/4.0/
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Neurosciences
Psychiatry
Neurosciences & Neurology
POSITRON-EMISSION-TOMOGRAPHY
METHYL-D-ASPARTATE
NMDA RECEPTOR HYPOFUNCTION
MEDIAL PREFRONTAL CORTEX
STRIATAL DOPAMINE
IN-VIVO
NUCLEUS-ACCUMBENS
PSYCHOTIC SYMPTOMS
SYNTHESIS CAPACITY
HEALTHY HUMANS
11 Medical And Health Sciences
06 Biological Sciences
17 Psychology And Cognitive Sciences
Psychiatry
Publication Status: Published
Appears in Collections:Clinical Sciences
Imaging Sciences
Faculty of Medicine



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