PT - JOURNAL ARTICLE AU - Hanna Antila AU - Maria Ryazantseva AU - Dina Popova AU - Pia Sipilä AU - Ramon Guirado AU - Samuel Kohtala AU - Ipek Yalcin AU - Jesse Lindholm AU - Liisa Vesa AU - Vinicius Sato AU - Joshua Cordeira AU - Henri Autio AU - Mikhail Kislin AU - Maribel Rios AU - Sâmia Joca AU - Plinio Casarotto AU - Leonard Khiroug AU - Sari Lauri AU - Tomi Taira AU - Eero Castrén AU - Tomi Rantamäki TI - Isoflurane produces antidepressant effects and induces TrkB signaling in rodents AID - 10.1101/084525 DP - 2017 Jan 01 TA - bioRxiv PG - 084525 4099 - http://biorxiv.org/content/early/2017/07/11/084525.short 4100 - http://biorxiv.org/content/early/2017/07/11/084525.full AB - 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.