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3,4-methylenedioxymethamphetamine (MDMA) impairs the extinction and reconsolidation of fear memory in rats.
Physiol Behav. 2019 02 01; 199:343-350.PB

Abstract

Clinical trials have demonstrated that 3,4-methylenedioxymethamphetamine (MDMA) paired with psychotherapy is more effective at reducing symptoms of post-traumatic stress disorder (PTSD) than psychotherapy or pharmacotherapy, alone or in combination. The processes through which MDMA acts to enhance psychotherapy are not well understood. Given that fear memories contribute to PTSD symptomology, MDMA could augment psychotherapy by targeting fear memories. The current studies investigated the effects of a single administration of MDMA on extinction and reconsolidation of cued and contextual fear memory in adult, male Long-Evans rats. Rats were exposed to contextual or auditory fear conditioning followed by systemic administration of saline or varying doses of MDMA (between 1 and 10 mg/kg) either 30 min before fear extinction training or immediately after brief fear memory retrieval (i.e. during the reconsolidation phase). MDMA administered prior to fear extinction training failed to enhance fear extinction memory, and in fact impaired drug-free cued fear extinction recall without impacting later fear relapse. MDMA administered during the reconsolidation phase, but not outside of the reconsolidation phase, produced a delayed and persistent reduction in conditioned fear. These findings are consistent with a general memory-disrupting effect of MDMA and suggest that MDMA could augment psychotherapy by modifying fear memories during reconsolidation without necessarily enhancing their extinction.

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Authors+Show Affiliations

Hake HS
Department of Psychology, University of Colorado Denver, PO Box 173364, Denver, CO 80217-3364, USA. Electronic address: holly.hake@ucdenver.edu.
Davis JKP
Department of Psychology, University of Colorado Denver, PO Box 173364, Denver, CO 80217-3364, USA. Electronic address: jazmyne.davis@ucdenver.edu.
Wood RR
Department of Psychology, University of Colorado Denver, PO Box 173364, Denver, CO 80217-3364, USA. Electronic address: river.wood@ucdenver.edu.
Tanner MK
Department of Psychology, University of Colorado Denver, PO Box 173364, Denver, CO 80217-3364, USA. Electronic address: margaret.tanner@ucdenver.edu.
Loetz EC
Department of Psychology, University of Colorado Denver, PO Box 173364, Denver, CO 80217-3364, USA. Electronic address: esteban.loetz@ucdenver.edu.
Sanchez A
Department of Psychology, University of Colorado Denver, PO Box 173364, Denver, CO 80217-3364, USA. Electronic address: anais.sanchez@ucdenver.edu.
Ostrovskyy M
Department of Psychology, University of Colorado Denver, PO Box 173364, Denver, CO 80217-3364, USA. Electronic address: mykola.ostrovskyy@ucdenver.edu.
Oleson EB
Department of Psychology, University of Colorado Denver, PO Box 173364, Denver, CO 80217-3364, USA. Electronic address: erik.oleson@ucdenver.edu.
Grigsby J
Department of Psychology, University of Colorado Denver, PO Box 173364, Denver, CO 80217-3364, USA; Department of Medicine, University of Colorado Denver School of Medicine, Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: jim.grigsby@ucdenver.edu.
Doblin R
Multidisciplinary Association for Psychedelic Studies, 1115 Mission Street, Santa Cruz, CA 95060-9989, USA.
Greenwood BN
Department of Psychology, University of Colorado Denver, PO Box 173364, Denver, CO 80217-3364, USA. Electronic address: benjamin.greenwood@ucdenver.edu.

MeSH

AnimalsConditioning, PsychologicalCuesExtinction, PsychologicalFearMaleMemoryMemory ConsolidationN-Methyl-3,4-methylenedioxyamphetamineRatsRats, Long-EvansSerotonin Agents

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30529341

Citation

Hake, Holly S., et al. "3,4-methylenedioxymethamphetamine (MDMA) Impairs the Extinction and Reconsolidation of Fear Memory in Rats." Physiology & Behavior, vol. 199, 2019, pp. 343-350.
Hake HS, Davis JKP, Wood RR, et al. 3,4-methylenedioxymethamphetamine (MDMA) impairs the extinction and reconsolidation of fear memory in rats. Physiol Behav. 2019;199:343-350.
Hake, H. S., Davis, J. K. P., Wood, R. R., Tanner, M. K., Loetz, E. C., Sanchez, A., Ostrovskyy, M., Oleson, E. B., Grigsby, J., Doblin, R., & Greenwood, B. N. (2019). 3,4-methylenedioxymethamphetamine (MDMA) impairs the extinction and reconsolidation of fear memory in rats. Physiology & Behavior, 199, 343-350. https://doi.org/10.1016/j.physbeh.2018.12.007
Hake HS, et al. 3,4-methylenedioxymethamphetamine (MDMA) Impairs the Extinction and Reconsolidation of Fear Memory in Rats. Physiol Behav. 2019 02 1;199:343-350. PubMed PMID: 30529341.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 3,4-methylenedioxymethamphetamine (MDMA) impairs the extinction and reconsolidation of fear memory in rats. AU - Hake,Holly S, AU - Davis,Jazmyne K P, AU - Wood,River R, AU - Tanner,Margaret K, AU - Loetz,Esteban C, AU - Sanchez,Anais, AU - Ostrovskyy,Mykola, AU - Oleson,Erik B, AU - Grigsby,Jim, AU - Doblin,Rick, AU - Greenwood,Benjamin N, Y1 - 2018/12/04/ PY - 2018/03/07/received PY - 2018/11/30/revised PY - 2018/12/03/accepted PY - 2018/12/12/pubmed PY - 2020/3/20/medline PY - 2018/12/12/entrez KW - Fear conditioning KW - Fear extinction KW - Fear memory KW - Post-traumatic stress disorder KW - Reconsolidation KW - Renewal SP - 343 EP - 350 JF - Physiology & behavior JO - Physiol Behav VL - 199 N2 - Clinical trials have demonstrated that 3,4-methylenedioxymethamphetamine (MDMA) paired with psychotherapy is more effective at reducing symptoms of post-traumatic stress disorder (PTSD) than psychotherapy or pharmacotherapy, alone or in combination. The processes through which MDMA acts to enhance psychotherapy are not well understood. Given that fear memories contribute to PTSD symptomology, MDMA could augment psychotherapy by targeting fear memories. The current studies investigated the effects of a single administration of MDMA on extinction and reconsolidation of cued and contextual fear memory in adult, male Long-Evans rats. Rats were exposed to contextual or auditory fear conditioning followed by systemic administration of saline or varying doses of MDMA (between 1 and 10 mg/kg) either 30 min before fear extinction training or immediately after brief fear memory retrieval (i.e. during the reconsolidation phase). MDMA administered prior to fear extinction training failed to enhance fear extinction memory, and in fact impaired drug-free cued fear extinction recall without impacting later fear relapse. MDMA administered during the reconsolidation phase, but not outside of the reconsolidation phase, produced a delayed and persistent reduction in conditioned fear. These findings are consistent with a general memory-disrupting effect of MDMA and suggest that MDMA could augment psychotherapy by modifying fear memories during reconsolidation without necessarily enhancing their extinction. SN - 1873-507X UR - https://www.unboundmedicine.com/medline/citation/30529341/34_methylenedioxymethamphetamine__MDMA__impairs_the_extinction_and_reconsolidation_of_fear_memory_in_rats_ DB - PRIME DP - Unbound Medicine ER -