Ketamine treatment upon memory retrieval reduces fear memory in marmoset monkeys

Philippens, I.H.C.H.M.; Draaisma, L.; Baarends, G.; Krugers, H.J.; Vermetten, E.

doi:doi:10.1016/j.euroneuro.2021.04.004

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...Show moreEmotionally 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/ )Show less

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Ketamine treatment upon memory retrieval reduces fear memory in marmoset monkeys