Ketamine treatment upon memory retrieval reduces fear memory in marmoset monkeys
| Autor: | Ingrid H.C.H.M. Philippens, Harm J. Krugers, Eric Vermetten, Laurijn Draaisma, Guus Baarends |
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| Přispěvatelé: | Structural and Functional Plasticity of the nervous system (SILS, FNWI) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Fear memory
Neurogenesis Inhibitory postsynaptic potential 03 medical and health sciences 0302 clinical medicine Memory biology.animal Heart rate Emotional memory Avoidance Learning Medicine Animals Pharmacology (medical) Ketamine Biological Psychiatry Memory Consolidation Non-human primates Pharmacology biology business.industry Marmoset Callithrix PTSD Fear 030227 psychiatry Psychiatry and Mental health Posttraumatic stress Neurology Neurology (clinical) Passive avoidance business Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | European Neuropsychopharmacology, 50, 1-11. Elsevier European Neuropsychopharmacology, 50, 1-11. ELSEVIER |
| ISSN: | 0924-977X |
| Popis: | Emotionally arousing experiences are retained very well as seen in posttraumatic stress disorder (PTSD). Various lines of evidence indicate that reactivation of these memories renders them labile which offers a potential time-window for intervention. We tested in non-human primates whether ketamine, administered during fear memory reactivation, affected passive (inhibitory) avoidance learning. For the consolidation of contextual emotional memory, the unescapable foot-shock paradigm in a passive avoidance task with two compartments (dark vs illuminated) was used. After entering the dark compartment, marmoset monkeys received four random foot-shocks (1 mA, 4 s) within 15-min. This stressful exposure increased the saliva cortisol and heart rate and impaired REM-sleep ( p < 0.05). One week later the monkeys were re-exposed to the stressful situation for the reconsolidation of the fearful experience. During the re-exposure the monkeys were treated with ketamine (0.5 mg/kg) or saline. In week 3, the monkeys were placed in the experimental setting to test their memory for the fearful experience. In contrast to the vehicle-treated monkeys, who avoided the dark compartment, the ketamine-treated monkeys entered the dark compartment that was previously associated with the fearful experience ( p < 0.05). Post-mortem analysis of the hippocampus showed that ketamine-treated animals exhibited less doublecortin positive neurons and BrdU-labeled cells in the dentate gyrus. This study reveals that a single low dose of ketamine, administered upon fear retrieval in monkeys, reduce contextual fear memory and attenuate neurogenesis in the hippocampus. These are important findings for considering ketamine as a potential candidate to target traumatic memories in PTSD. (c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ) |
| Databáze: | OpenAIRE |
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