PMID- 30529341 OWN - NLM STAT- MEDLINE DCOM- 20200319 LR - 20231012 IS - 1873-507X (Electronic) IS - 0031-9384 (Print) IS - 0031-9384 (Linking) VI - 199 DP - 2019 Feb 1 TI - 3,4-methylenedioxymethamphetamine (MDMA) impairs the extinction and reconsolidation of fear memory in rats. PG - 343-350 LID - S0031-9384(18)31097-7 [pii] LID - 10.1016/j.physbeh.2018.12.007 [doi] AB - 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. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Hake, Holly S AU - Hake HS AD - Department of Psychology, University of Colorado Denver, PO Box 173364, Denver, CO 80217-3364, USA. Electronic address: holly.hake@ucdenver.edu. FAU - Davis, Jazmyne K P AU - Davis JKP AD - Department of Psychology, University of Colorado Denver, PO Box 173364, Denver, CO 80217-3364, USA. Electronic address: jazmyne.davis@ucdenver.edu. FAU - Wood, River R AU - Wood RR AD - Department of Psychology, University of Colorado Denver, PO Box 173364, Denver, CO 80217-3364, USA. Electronic address: river.wood@ucdenver.edu. FAU - Tanner, Margaret K AU - Tanner MK AD - Department of Psychology, University of Colorado Denver, PO Box 173364, Denver, CO 80217-3364, USA. Electronic address: margaret.tanner@ucdenver.edu. FAU - Loetz, Esteban C AU - Loetz EC AD - Department of Psychology, University of Colorado Denver, PO Box 173364, Denver, CO 80217-3364, USA. Electronic address: esteban.loetz@ucdenver.edu. FAU - Sanchez, Anais AU - Sanchez A AD - Department of Psychology, University of Colorado Denver, PO Box 173364, Denver, CO 80217-3364, USA. Electronic address: anais.sanchez@ucdenver.edu. FAU - Ostrovskyy, Mykola AU - Ostrovskyy M AD - Department of Psychology, University of Colorado Denver, PO Box 173364, Denver, CO 80217-3364, USA. Electronic address: mykola.ostrovskyy@ucdenver.edu. FAU - Oleson, Erik B AU - Oleson EB AD - Department of Psychology, University of Colorado Denver, PO Box 173364, Denver, CO 80217-3364, USA. Electronic address: erik.oleson@ucdenver.edu. FAU - Grigsby, Jim AU - Grigsby J AD - 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. FAU - Doblin, Rick AU - Doblin R AD - Multidisciplinary Association for Psychedelic Studies, 1115 Mission Street, Santa Cruz, CA 95060-9989, USA. FAU - Greenwood, Benjamin N AU - Greenwood BN AD - Department of Psychology, University of Colorado Denver, PO Box 173364, Denver, CO 80217-3364, USA. Electronic address: benjamin.greenwood@ucdenver.edu. LA - eng GR - R15 MH114026/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20181204 PL - United States TA - Physiol Behav JT - Physiology & behavior JID - 0151504 RN - 0 (Serotonin Agents) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) SB - IM MH - Animals MH - Conditioning, Psychological/*drug effects MH - Cues MH - Extinction, Psychological/*drug effects MH - Fear MH - Male MH - Memory/drug effects MH - Memory Consolidation/*drug effects MH - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology MH - Rats MH - Rats, Long-Evans MH - Serotonin Agents/*pharmacology PMC - PMC6557441 MID - NIHMS1516335 OTO - NOTNLM OT - Fear conditioning OT - Fear extinction OT - Fear memory OT - Post-traumatic stress disorder OT - Reconsolidation OT - Renewal EDAT- 2018/12/12 06:00 MHDA- 2020/03/20 06:00 PMCR- 2020/02/01 CRDT- 2018/12/12 06:00 PHST- 2018/03/07 00:00 [received] PHST- 2018/11/30 00:00 [revised] PHST- 2018/12/03 00:00 [accepted] PHST- 2018/12/12 06:00 [pubmed] PHST- 2020/03/20 06:00 [medline] PHST- 2018/12/12 06:00 [entrez] PHST- 2020/02/01 00:00 [pmc-release] AID - S0031-9384(18)31097-7 [pii] AID - 10.1016/j.physbeh.2018.12.007 [doi] PST - ppublish SO - Physiol Behav. 2019 Feb 1;199:343-350. doi: 10.1016/j.physbeh.2018.12.007. Epub 2018 Dec 4.