Rapid-acting antidepressants and the regulation of TrkB neurotrophic signalling-Insights from ketamine, nitrous oxide, seizures and anaesthesia

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Kohtala , S & Rantamäki , T 2021 , ' Rapid-acting antidepressants and the regulation of TrkB neurotrophic signalling-Insights from ketamine, nitrous oxide, seizures and anaesthesia ' , Basic & Clinical Pharmacology & Toxicology , vol. 129 , no. 2 , pp. 95-103 . https://doi.org/10.1111/bcpt.13598

Title: Rapid-acting antidepressants and the regulation of TrkB neurotrophic signalling-Insights from ketamine, nitrous oxide, seizures and anaesthesia
Author: Kohtala, Samuel; Rantamäki, Tomi
Contributor: University of Helsinki, Division of Pharmacology and Pharmacotherapy
University of Helsinki, Drug Research Program
Date: 2021-08
Language: eng
Number of pages: 9
Belongs to series: Basic & Clinical Pharmacology & Toxicology
ISSN: 1742-7835
URI: http://hdl.handle.net/10138/333425
Abstract: Increased glutamatergic neurotransmission and synaptic plasticity in the prefrontal cortex have been associated with the rapid antidepressant effects of ketamine. Activation of BDNF (brain-derived neurotrophic factor) receptor TrkB is considered a key molecular event for antidepressant-induced functional and structural synaptic plasticity. Several mechanisms have been proposed to underlie ketamine's effects on TrkB, but much remains unclear. Notably, preliminary studies suggest that besides ketamine, nitrous oxide (N2O) can rapidly alleviate depressive symptoms. We have shown nitrous oxide to evoke TrkB signalling preferentially after the acute pharmacological effects have dissipated (ie after receptor disengagement), when slow delta frequency electroencephalogram (EEG) activity is up-regulated. Our findings also demonstrate that various anaesthetics and sedatives activate TrkB signalling, further highlighting the complex mechanisms underlying TrkB activation. We hypothesize that rapid-acting antidepressants share the ability to regulate TrkB signalling during homeostatically evoked slow-wave activity and that this mechanism is important for sustained antidepressant effects. Our observations urge the examination of rapid and sustained antidepressant effects beyond conventional receptor pharmacology by focusing on brain physiology and temporally distributed signalling patterns spanning both wake and sleep. Potential implications of this approach for the improvement of current therapies and discovery of novel antidepressants are discussed.
Subject: electroencephalogram
energy metabolism
protein phosphorylation
rapid&#8208
acting antidepressant
sleep
ELECTROCONVULSIVE-THERAPY
MESSENGER-RNA
RAT-BRAIN
DEPRESSION
SLEEP
PLASTICITY
CONSOLIDATION
HOMEOSTASIS
BDNF
3112 Neurosciences
317 Pharmacy
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