3,4-Methylenedioxymethamphetamine facilitates fear extinction learning
Matthew B Young, Raül Andero, Kerry J. Ressler, Leonard L. Howell
Translational Psychiatry September 15, 2015 DOI: 10.1038/tp.2015.138 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | MDMA |
| Dose | 7.8 mg kg −1 |
| Topics | Anxiety MDMA |
| Keywords | Extinction optical mineralogy Basolateral amygdala Prefrontal cortex Exposure therapy Fear conditioning Cognition |
| Citations | 137 |
| Post-publication review | 1 comment on PubPeer (opens in new tab) · last active December 2015 |
| Key findings | MDMA enhances fear memory extinction through a BDNF-dependent mechanism in mice. |
Abstract
Abstract Acutely administered 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) has been proposed to have long-term positive effects on post-traumatic stress disorder (PTSD) symptoms when combined with psychotherapy. No preclinical data support a mechanistic basis for these claims. Given the persistent nature of psychotherapeutic gains facilitated by MDMA, we hypothesized that MDMA improves fear extinction learning, a key process in exposure-based therapies for PTSD. In these experiments, mice were first exposed to cued fear conditioning and treated with drug vehicle or MDMA before extinction training 2 days later. MDMA was administered systemically and also directly targeted to brain structures known to contribute to extinction. In addition to behavioral measures of extinction, changes in mRNA levels of brain-derived neurotrophic factor ( Bdnf ) and Fos were measured after MDMA treatment and extinction. MDMA (7.8 mg kg −1 ) persistently and robustly enhanced long-term extinction when administered before extinction training. MDMA increased the expression of Fos in the amygdala and medial prefrontal cortex (mPFC), whereas increases in Bdnf expression were observed only in the amygdala after extinction training. Extinction enhancements were recapitulated when MDMA (1 μg) was infused directly into the basolateral complex of the amygdala (BLA), and enhancement was abolished when BDNF signaling was inhibited before extinction. These findings suggest that MDMA enhances fear memory extinction through a BDNF-dependent mechanism, and that MDMA may be a useful adjunct to exposure-based therapies for PTSD and other anxiety disorders characterized by altered fear learning.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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MDMA persistently enhanced long-term fear extinction learning through a BDNF-dependent mechanism in the amygdala.
Synthesized
Comparable studies
Other preclinical and animal studies on MDMA for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Effects of acute social stress on the conditioned place preference induced by MDMA in adolescent and adult mice Adolescent (postnatal day 29-40) and adult (postnatal day 50-61) male mice | 2014 | Experimental study | |
| MDMA in Adolescent Male Rats Adolescent male rats (postnatal day 45) | 2006 | Controlled experiment | n = 12 |
| Psychedelics: A review of their effects on recalled aversive memories and fear/anxiety expression in rodents Rodents | 2024 | Review | |
| Differential behavioral outcomes of 3,4-methylenedioxymethamphetamine (MDMA-ecstasy) in anxiety-like responses in mice 2-month-old Balb/c male mice (25-35 g) | 2013 | Observational study | n = 70 |
| Methylone is a rapid-acting neuroplastogen with less off-target activity than MDMA Rats | 2024 | Preclinical study |