Isoflurane produces antidepressant effects and induces TrkB signaling in rodents

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  • Hanna Antila, Neuroscience Center, University of Helsinki, P.O. Box 56, Helsinki, FI-00014, Finland.
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  • Maria Ryazantseva, Division of Physiology and Neuroscience, Department of Biosciences, Faculty of Biological and Environmental Sciences, University of Helsinki, P.O. Box 66, Helsinki, FI-00014, Finland.
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  • Dina Popova, Neuroscience Center, University of Helsinki, P.O. Box 56, Helsinki, FI-00014, Finland.
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  • Pia Sipilä, Neuroscience Center, University of Helsinki, P.O. Box 56, Helsinki, FI-00014, Finland.
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  • Ramon Guirado, Neuroscience Center, University of Helsinki, P.O. Box 56, Helsinki, FI-00014, Finland.
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  • Samuel Kohtala, Division of Physiology and Neuroscience, Department of Biosciences, Faculty of Biological and Environmental Sciences, University of Helsinki, P.O. Box 66, Helsinki, FI-00014, Finland.
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  • Ipek Yalcin, Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique, FR-67084, Strasbourg Cedex, France.
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  • Jesse Lindholm, Neuroscience Center, University of Helsinki, P.O. Box 56, Helsinki, FI-00014, Finland.
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  • Liisa Vesa, Neuroscience Center, University of Helsinki, P.O. Box 56, Helsinki, FI-00014, Finland.
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  • Vinicius Sato, School of Pharmaceutical Sciences of Ribeirão Preto, 14040-903, Ribeirão Preto, São Paulo, Brazil.
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  • Joshua Cordeira, Tufts University, Boston, USA
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  • Henri Autio, Neuroscience Center, University of Helsinki, P.O. Box 56, Helsinki, FI-00014, Finland.
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  • Mikhail Kislin, Neuroscience Center, University of Helsinki, P.O. Box 56, Helsinki, FI-00014, Finland.
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  • Maribel Rios, Tufts University, Boston, USA
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  • Sâmia Joca
  • Plinio Casarotto, Neuroscience Center, University of Helsinki, P.O. Box 56, Helsinki, FI-00014, Finland.
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  • Leonard Khiroug, Neuroscience Center, University of Helsinki, P.O. Box 56, Helsinki, FI-00014, Finland.
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  • Sari Lauri, Division of Physiology and Neuroscience, Department of Biosciences, Faculty of Biological and Environmental Sciences, University of Helsinki, P.O. Box 66, Helsinki, FI-00014, Finland.
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  • Tomi Taira, Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014, Helsinki, Finland.
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  • Eero Castrén, Neuroscience Center, University of Helsinki, P.O. Box 56, Helsinki, FI-00014, Finland. eero.castren@helsinki.fi.
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  • Tomi Rantamäki, Division of Physiology and Neuroscience, Department of Biosciences, Faculty of Biological and Environmental Sciences, University of Helsinki, P.O. Box 66, Helsinki, FI-00014, Finland. tomi.rantamaki@helsinki.fi.

A brief burst-suppressing isoflurane anesthesia has been shown to rapidly alleviate symptoms of depression in a subset of patients, but the neurobiological basis of these observations remains obscure. We show that a single isoflurane anesthesia produces antidepressant-like behavioural effects in the learned helplessness paradigm and regulates molecular events implicated in the mechanism of action of rapid-acting antidepressant ketamine: activation of brain-derived neurotrophic factor (BDNF) receptor TrkB, facilitation of mammalian target of rapamycin (mTOR) signaling pathway and inhibition of glycogen synthase kinase 3β (GSK3β). Moreover, isoflurane affected neuronal plasticity by facilitating long-term potentiation in the hippocampus. We also found that isoflurane increased activity of the parvalbumin interneurons, and facilitated GABAergic transmission in wild type mice but not in transgenic mice with reduced TrkB expression in parvalbumin interneurons. Our findings strengthen the role of TrkB signaling in the antidepressant responses and encourage further evaluation of isoflurane as a rapid-acting antidepressant devoid of the psychotomimetic effects and abuse potential of ketamine.

Original languageEnglish
JournalScientific Reports
Volume7
Issue1
Pages (from-to)7811
ISSN2045-2322
DOIs
Publication statusPublished - 10 Aug 2017

    Research areas

  • Journal Article

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