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Nitrous oxide speeds the reduction of distressing intrusive memories in an experimental model of psychological trauma

Published online by Cambridge University Press:  04 March 2016

R. K. Das ,
A. Tamman ,
V. Nikolova ,
T. P. Freeman ,
J. A. Bisby ,
A. I. Lazzarino  and
S. K. Kamboj
R. K. Das*
Affiliation:
Clinical Psychopharmacology Unit, UCL, London, UK
A. Tamman
Affiliation:
Clinical Psychopharmacology Unit, UCL, London, UK
V. Nikolova
Affiliation:
Clinical Psychopharmacology Unit, UCL, London, UK
T. P. Freeman
Affiliation:
Clinical Psychopharmacology Unit, UCL, London, UK
J. A. Bisby
Affiliation:
Institute of Cognitive Neuroscience, UCL, London, UK
A. I. Lazzarino
Affiliation:
London School of Hygiene & Tropical Medicine, London, UK Department of Epidemiology and Public Health, UCL, London, UK
S. K. Kamboj*
Affiliation:
Clinical Psychopharmacology Unit, UCL, London, UK
*
*Address for correspondence: Dr R. K. Das, Clinical Psychopharmacology Unit, UCL, 1–19 Torrington Place, London WC1E 7HB, UK. (Email: [email protected])
*Address for correspondence: Dr R. K. Das, Clinical Psychopharmacology Unit, UCL, 1–19 Torrington Place, London WC1E 7HB, UK. (Email: [email protected])
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Abstract

Background

Post-traumatic stress disorder (PTSD) involves maladaptive long-term memory formation which underlies involuntary intrusive thoughts about the trauma. Preventing the development of such maladaptive memory is a key aim in preventing the development of PTSD. We examined whether the N-methyl d-aspartate receptor (NMDAR) antagonist gas nitrous oxide (N2O) could reduce the frequency of intrusive memories by inhibiting NMDAR-dependent memory consolidation in a laboratory analogue of psychological trauma.

Method

Participants were randomized to inhale N2O (N = 25) or medical air (N = 25) after viewing a negatively valenced emotional film clip (‘trauma film’). Participants subsequently completed a daily diary assessing frequency of intrusive thoughts relating to the film clip. A week later, participants completed an explicit memory recall task related to the film.

Results

Post-encoding N2O sped the reduction in intrusive memory frequency, with a significant reduction by the next day in the N2O group compared to 4 days later in the air group. N2O also interacted with post-film dissociation, producing increased intrusion frequency in those who were highly dissociated at baseline. Sleep length and quality the night after viewing the film did not differ between the groups.

Conclusion

N2O speeds the reduction of intrusive analogue trauma memory in a time-dependent manner, consistent with sleep-dependent long-term consolidation disruption. Further research with this drug is warranted to determine its potential to inoculate against enduring effects of psychological trauma; however, caution is also urged in dissociated individuals where N2O may aggravate PTSD-like symptomatology.

Keywords

Intrusionsmemory consolidationnitrous oxidePTSD
Type
Original Articles
Information
Psychological Medicine , Volume 46 , Issue 8 , June 2016 , pp. 1749 - 1759
Copyright
Copyright © Cambridge University Press 2016 

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References

Amey, BD, Ballinger, JA, Harrison, EE (1981). Prehospital administration of nitrous oxide for control of pain. Annals of Emergency Medicine 10, 247–251.CrossRefGoogle ScholarPubMed
APA (2013). Diagnostic and Statistical Manual of Mental Disorders (DSM-5). American Psychiatric Association: Washington, D.C.Google Scholar
Baayen, RH, Davidson, DJ, Bates, DM (2008). Mixed-effects modeling with crossed random effects for subjects and items. Journal of Memory and Language 59, 390–412.CrossRefGoogle Scholar
Bates, DM (2010). lme4: Mixed-effects modeling with R (http://lme4.r-forge.r-project.org/book).Google Scholar
Beck, AT, Steer, RA, Carbin, MG (1988). Psychometric properties of the beck depression inventory: twenty-five years of evaluation. Clinical Psychology Review 8, 77–100.CrossRefGoogle Scholar
Bisby, JA, Brewin, CR, Leitz, JR, Curran, HV (2009). Acute effects of alcohol on the development of intrusive memories. Psychopharmacology 204, 655–666.CrossRefGoogle ScholarPubMed
Bliss, TV, Collingridge, GL (1993). A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361, 31–39.CrossRefGoogle ScholarPubMed
Bremner, JD, Krystal, JH, Putnam, FW, Southwick, SM, Marmar, C, Charney, DS, Mazure, CM (1998). Measurement of dissociative states with the clinician-administered dissociative states scale (CADSS). Journal of Traumatic Stress 11, 125–136.CrossRefGoogle ScholarPubMed
Brewin, CR (2001 a). A cognitive neuroscience account of posttraumatic stress disorder and its treatment. Behaviour Research and Therapy 39, 373–393.CrossRefGoogle ScholarPubMed
Brewin, CR (2001 b). Memory processes in post-traumatic stress disorder. International Review of Psychiatry 13, 159–163.CrossRefGoogle Scholar
Brewin, CR (2013). Episodic memory, perceptual memory, and their interaction: foundations for a theory of posttraumatic stress disorder. Psychological Bulletin 140, 69–97.Google Scholar
Brewin, CR, Dalgleish, T, Joseph, S (1996). A dual representation theory of posttraumatic stress disorder. Psychological Review 103, 670.CrossRefGoogle ScholarPubMed
Briere, J, Scott, C, Weathers, F (2014). Peritraumatic and persistent dissociation in the presumed etiology of PTSD. American Journal of Psychiatry 162, 2295–2301.CrossRefGoogle Scholar
Carlson, EB, Putnam, FW (1993). An update on the dissociative experiences scale. Dissociation: Progress in the Dissociative Disorders 6, 16–27.Google Scholar
Cohen, S, Kozlovsky, N, Matar, MA, Kaplan, Z, Zohar, J, Cohen, H (2012). Post-exposure sleep deprivation facilitates correctly timed interactions between glucocorticoid and adrenergic systems, which attenuate traumatic stress responses. Neuropsychopharmacology 37, 2388–2404.CrossRefGoogle ScholarPubMed
Das, RK, Freeman, TP, Kamboj, SK (2013). The effects of N-methyl d-aspartate and B-adrenergic receptor antagonists on the reconsolidation of reward memory: a meta-analysis. Neuroscience & Biobehavioral Reviews 37, 240–255.CrossRefGoogle ScholarPubMed
Diekelmann, S, Born, J (2010). The memory function of sleep. Nature Reviews Neuroscience 11, 114–126.CrossRefGoogle ScholarPubMed
Dunsmoor, JE, Murty, VP, Davachi, L, Phelps, EA (2015). Emotional learning selectively and retroactively strengthens memories for related events. Nature 520, 345–348.CrossRefGoogle ScholarPubMed
Ehlers, A, Hackmann, A, Michael, T (2004). Intrusive re-experiencing in post-traumatic stress disorder: phenomenology, theory, and therapy. Memory 12, 403–415.CrossRefGoogle ScholarPubMed
Emmanouil, DE, Quock, RM (2007). Advances in understanding the actions of nitrous oxide. Anesthesia Progress 54, 9–18.CrossRefGoogle ScholarPubMed
Feder, A, Parides, MK, Murrough, JW, Perez, AM, Morgan, JE, Saxena, S, Kirkwood, K, Aan Het Rot, M, Lapidus, KA, Wan, L-B (2014). Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiatry 71, 681–688.CrossRefGoogle ScholarPubMed
Fisher, JD, Brown, SN, Cooke, MW, Committee, JRCAL, Association, AS, Wales, N, Ireland, N (2006). UK Ambulance Service clinical practice guidelines. London: Joint Royal College Ambulance Liaison Committee.Google Scholar
Frey, U, Morris, RG (1997). Synaptic tagging and long-term potentiation. Nature 385, 533–536.CrossRefGoogle ScholarPubMed
Gais, S, Born, J (2004). Declarative memory consolidation: mechanisms acting during human sleep. Learning & Memory 11, 679–685.CrossRefGoogle ScholarPubMed
Hackmann, A, Ehlers, A, Speckens, A, Clark, D (2004). Characteristics and content of intrusive memories in PTSD and their changes with treatment. Journal of Traumatic Stress 17, 231–240.CrossRefGoogle ScholarPubMed
Halligan, SL, Michael, T, Clark, DM, Ehlers, A (2003). Posttraumatic stress disorder following assault: the role of cognitive processing, trauma memory, and appraisals. Journal of Consulting and Clinical Psychology 71, 419.CrossRefGoogle ScholarPubMed
Hellawell, SJ, Brewin, CR (2004). A comparison of flashbacks and ordinary autobiographical memories of trauma: content and language. Behaviour Research and Therapy 42, 1–12.CrossRefGoogle ScholarPubMed
Holmes, EA, James, EL, Coode-Bate, T, Deeprose, C (2009). Can playing the computer game ‘Tetris’ reduce the build-up of flashbacks for trauma?: a proposal from cognitive science. PLoS ONE 4, e4153.CrossRefGoogle ScholarPubMed
Holmes, EA, James, EL, Kilford, EJ, Deeprose, C (2010). Key steps in developing a cognitive vaccine against traumatic flashbacks: visuospatial tetris versus verbal pub quiz. PLoS ONE 5, e13706.Google ScholarPubMed
James, EL, Bonsall, MB, Hoppitt, L, Tunbridge, EM, Geddes, JR, Milton, AL, Holmes, EA (2015). Computer game play reduces intrusive memories of experimental trauma via reconsolidation-update mechanisms. Psychological Science 26, 1201–1215.CrossRefGoogle ScholarPubMed
Jevtović-Todorović, V, Todorovć, S, Mennerick, S, Powell, S, Dikranian, K, Benshoff, N, Zorumski, C, Olney, J (1998). Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin. Nature Medicine 4, 460–463.CrossRefGoogle ScholarPubMed
Jevtovic-Todorovic, V, Wozniak, DF, Benshoff, ND, Olney, JW (2001). A comparative evaluation of the neurotoxic properties of ketamine and nitrous oxide. Brain Research 895, 264–267.CrossRefGoogle ScholarPubMed
Ji, D, Wilson, MA (2007). Coordinated memory replay in the visual cortex and hippocampus during sleep. Nature Neuroscience 10, 100–107.CrossRefGoogle ScholarPubMed
Jones, M, Errington, M, French, P, Fine, A, Bliss, T, Garel, S, Charnay, P, Bozon, B, Laroche, S, Davis, S (2001). A requirement for the immediate early gene Zif268 in the expression of late LTP and long-term memories. Nature Neuroscience 4, 289–296.CrossRefGoogle ScholarPubMed
Lahti, T, Methuen, T, Roine, R, Seppa, KL, Sinclair, D, Partinen, M, Alho, H (2011). The impacts of nitrous oxide gas on sleep quality during alcohol withdrawal. BMC Research Notes 4, 108.CrossRefGoogle ScholarPubMed
McGaugh, JL (2004). The amygdala modulates the consolidation of memories of emotionally arousing experiences. Annual Review of Neuroscience 27, 1–28.CrossRefGoogle ScholarPubMed
Michael, T, Ehlers, A, Halligan, S, Clark, D (2005). Unwanted memories of assault: what intrusion characteristics are associated with PTSD?. Behaviour Research and Therapy 43, 613–628.CrossRefGoogle ScholarPubMed
Murray, J, Ehlers, A, Mayou, RA (2002). Dissociation and post-traumatic stress disorder: two prospective studies of road traffic accident survivors. British Journal of Psychiatry 180, 363–368.CrossRefGoogle ScholarPubMed
O'Donnell, ML, Creamer, M, Pattison, P (2004). Posttraumatic stress disorder and depression following trauma: understanding comorbidity. American Journal of Psychiatry 161, 1390–1396.CrossRefGoogle ScholarPubMed
O'Sullivan, Í, Benger, J (2003). Nitrous oxide in emergency medicine. Emergency Medicine Journal 20, 214–217.CrossRefGoogle ScholarPubMed
Payne, JD, Nadel, L (2004). Sleep, dreams, and memory consolidation: the role of the stress hormone cortisol. Learning & Memory 11, 671–678.CrossRefGoogle ScholarPubMed
Porcheret, K, Holmes, EA, Goodwin, GM, Foster, RG, Wulff, K (2015). Psychological effect of an analogue traumatic event reduced by sleep deprivation. Sleep 38, 1017–1025.CrossRefGoogle ScholarPubMed
Porges, SW (1997). Emotion: an evolutionary by-product of the neural regulation of the autonomic nervous systema. Annals of the New York Academy of Sciences 807, 62–77.CrossRefGoogle Scholar
R Core Development Team (2014). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing: Vienna, Austria, 2012.Google Scholar
Rasch, B, Büchel, C, Gais, S, Born, J (2007). Odor cues during slow-wave sleep prompt declarative memory consolidation. Science 315, 1426–1429.CrossRefGoogle ScholarPubMed
Roozendaal, B (2000). Glucocorticoids and the regulation of memory consolidation. Psychoneuroendocrinology 25, 213–238.CrossRefGoogle ScholarPubMed
Roozendaal, B (2002). Stress and memory: opposing effects of glucocorticoids on memory consolidation and memory retrieval. Neurobiology of Learning and Memory 78, 578–595.CrossRefGoogle ScholarPubMed
Roozendaal, B, Quirarte, GL, McGaugh, JL (2002). Glucocorticoids interact with the basolateral amygdala β-adrenoceptor–cAMP/cAMP/PKA system in influencing memory consolidation. European Journal of Neuroscience 15, 553–560.CrossRefGoogle ScholarPubMed
Sajikumar, S, Frey, JU (2004). Late-associativity, synaptic tagging, and the role of dopamine during LTP and LTD. Neurobiology of Learning and Memory 82, 12–25.CrossRefGoogle ScholarPubMed
Schönenberg, M, Reichwald, U, Domes, G, Badke, A, Hautzinger, M (2005). Effects of peritraumatic ketamine medication on early and sustained posttraumatic stress symptoms in moderately injured accident victims. Psychopharmacology 182, 420–425.CrossRefGoogle ScholarPubMed
Schönenberg, M, Reichwald, U, Domes, G, Badke, A, Hautzinger, M (2008). Ketamine aggravates symptoms of acute stress disorder in a naturalistic sample of accident victims. Journal of Psychopharmacology 22, 493–497.CrossRefGoogle Scholar
Shimizu, E, Tang, Y-P, Rampon, C, Tsien, JZ (2000). NMDA receptor-dependent synaptic reinforcement as a crucial process for memory consolidation. Science 290, 1170–1174.CrossRefGoogle ScholarPubMed
Simons, JS, Gaher, RM (2005). The distress tolerance scale: development and validation of a self-report measure. Motivation and Emotion 29, 83–102.CrossRefGoogle Scholar
Solomon, SD, Davidson, JR (1997). Trauma: prevalence, impairment, service use, and cost. Journal of Clinical Psychiatry 58, S5–11.Google ScholarPubMed
Soni, M, Curran, VH, Kamboj, SK (2013). Identification of a narrow post-ovulatory window of vulnerability to distressing involuntary memories in healthy women. Neurobiology of Learning and Memory 104, 32–38.CrossRefGoogle ScholarPubMed
Stickgold, R (2005). Sleep-dependent memory consolidation. Nature 437, 1272–1278.CrossRefGoogle ScholarPubMed
Tarvainen, M, Niskanen, JP, Lipponen, JA, Ranta-aho, PO, Karjalainen, PA (2009). Kubios HRV– a software for advanced heart rate variability analysis. In 4th European Conference of the International Federation for Medical and Biological Engineering (ed. Vander, J. Sloten, , Verdonck, P., Nyssen, M. and Haueisen, J.), pp. 1022–1025. Springer: Berlin Heidelberg.CrossRefGoogle Scholar
Van der Kolk, BA, Fisler, R (1995). Dissociation and the fragmentary nature of traumatic memories: overview and exploratory study. Journal of Traumatic Stress 8, 505–525.CrossRefGoogle ScholarPubMed
Van der Kolk, BA, McFarlane, AC, Weisaeth, L (1996). Traumatic Stress. Guilford: New York.Google Scholar
Verwoerd, J, de Jong, P, Wessel, I (2008). Low attentional control and the development of intrusive memories following a laboratory stressor. Journal of Psychopathology and Behavioral Assessment 30, 291–297.CrossRefGoogle Scholar