3,4-methylenedioxymethamphetamine (MDMA) impairs the extinction and reconsolidation of fear memory in rats. 2019

Holly S Hake, and Jazmyne K P Davis, and River R Wood, and Margaret K Tanner, and Esteban C Loetz, and Anais Sanchez, and Mykola Ostrovskyy, and Erik B Oleson, and Jim Grigsby, and Rick Doblin, and Benjamin N Greenwood
Department of Psychology, University of Colorado Denver, PO Box 173364, Denver, CO 80217-3364, USA. Electronic address: holly.hake@ucdenver.edu.

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.

UI MeSH Term Description Entries
D008297 Male Males
D008568 Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory.
D003213 Conditioning, Psychological Simple form of learning involving the formation, strengthening, or weakening of an association between a stimulus and a response. Conditioning, Psychology,Psychological Conditioning,Social Learning Theory,Social Learning Theories,Theory, Social Learning
D003463 Cues Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. Cue
D005108 Extinction, Psychological The procedure of presenting the conditioned stimulus without REINFORCEMENT to an organism previously conditioned. It refers also to the diminution of a conditioned response resulting from this procedure. Psychological Extinction,Extinction (Psychology),Extinctions (Psychology),Extinctions, Psychological,Psychological Extinctions
D005239 Fear The affective response to an actual current external danger which subsides with the elimination of the threatening condition. Threat Cues,Threat Sensitivity,Cue, Threat,Fears,Sensitivity, Threat,Threat Cue,Threat Sensitivities
D000069077 Memory Consolidation Neurological process involving the conversion of learned information into long-term memory. Consolidation, Memory,Consolidations, Memory,Memory Consolidations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D018490 Serotonin Agents Drugs used for their effects on serotonergic systems. Among these are drugs that affect serotonin receptors, the life cycle of serotonin, and the survival of serotonergic neurons. Serotonergic Agents,Serotonergic Drugs,Serotonin Drugs,Serotonin Effect,Serotonin Effects,Serotoninergic Effect,Serotoninergic Effects,Agents, Serotonergic,Agents, Serotonin,Drugs, Serotonergic,Drugs, Serotonin,Effect, Serotonin,Effect, Serotoninergic,Effects, Serotonin,Effects, Serotoninergic

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