Behavioral and neurochemical consequences of multiple MDMA administrations in the rat: role of individual differences in anxiety-related behavior.
V Ludwig, Y Mihov, R K W Schwarting
Behavioural Brain Research May 16, 2008 DOI: 10.1016/j.bbr.2007.12.008 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Male Wistar rats classified as high-anxiety or low-anxiety based on elevated plus-maze screening |
| Interventions | MDMA saline |
| Dose | 5 mg/kg |
| Duration | Five daily injections, followed by a test battery including an MDMA challenge, elevated plus-maze retest, novel-object test, and final neurochemical analysis |
| Measures | elevated plus-maze (EPM), novel-object test, neurochemical analysis of serotonin and dopamine |
| Topics | Anxiety MDMA |
| Key findings | Repeated low-dose MDMA (5 mg/kg daily for five days) produced behavioral sensitization and outlasting behavioral changes, particularly in low-anxiety rats, which showed more open-arm time, locomotion, and novel-object exploration. Repeated MDMA also led to moderately lower serotonin in the ventral striatum and higher dopamine in the frontal cortex compared with single MDMA, with effects moderated by individual anxiety-related differences. |
Abstract
Using the elevated plus-maze (EPM), Wistar rats can be distinguished into high (HA) or low anxiety (LA) subjects. These differences seem to reflect traits, since HA and LA rats vary also in other anxiety-dependent tasks, neurochemical mechanisms, and psychopharmacological reactivity, including lasting consequences after single treatment with 3,4-methylenedioxymethamphetamine (MDMA). Here, we tested whether multiple MDMA treatments also have subject-dependent effects. Based on routine EPM screening, male Wistar rats were divided into HA and LA sub-groups, which received five (i.e. multiple) daily injections of MDMA (5 mg/kg) or saline, followed by a test battery, including a challenge test with MDMA, a retest in the EPM, a novel-object test, and a final neurochemical analysis. Acutely, MDMA led to comparable hyperactivity in HA and LA rats. After multiple MDMA, behavioral sensitization was observed, especially in LA rats. Open arm time during the EPM retest (min 0-5) correlated with that of the initial one only in those rats, which had received a single injection of MDMA. Rats with multiple MDMA, especially LA-rats, showed more open-arm time and locomotion during the subsequent 5-10 min of the retest. In a novel-object test, rats with multiple MDMA, again especially LA subjects, showed more exploratory bouts towards the novel object. Neurochemically, multiple MDMA led to moderately lower serotonin in the ventral striatum, and higher dopamine levels in the frontal cortex as compared to single MDMA; these effects were also moderated by subject-dependent factors. Our data show that low-dosed multiple MDMA can lead to behavioral sensitization and outlasting consequences, which affect behavior in the EPM and a novel object task. Detecting such sequels partly requires consideration of individual differences.
Comparable studies
Other preclinical and animal studies on MDMA for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| 3,4-Methylenedioxymethamphetamine facilitates fear extinction learning Mice | 2015 | Preclinical experimental study | |
| 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 |
Citations in the library
Cited by 10
- Sex-Dependent Psychoneuroendocrine Effects of THC and MDMA in an Animal Model of Adolescent Drug Consumption PLoS One November 4, 2013
- MDMA (3,4-Methylenedioxymethamphetamine) Analogues as Tools to Characterize MDMA-Like Effects: An Approach to Understand Entactogen Pharmacology Current Neuropharmacology August 1, 2013
- Psychedelics: A review of their effects on recalled aversive memories and fear/anxiety expression in rodents Neuroscience & Biobehavioral Reviews September 20, 2024
- Examining the Role of Oxytocinergic Signaling and Neuroinflammatory Markers in the Therapeutic Effects of MDMA in a Rat Model for PTSD. Pharmaceuticals June 27, 2024
- A repeated low-dose regimen of MDMA has transient next-day effects on locomotor activity, anxiety-like behavior, and brain serotonin levels, with no effect on anhedonia-like behavior, in both female and male rats Psychopharmacology March 4, 2026
and 5 more in the library
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- 3,4‐Methylenedioxymethamphetamine (MDMA, “Ecstasy”): pharmacology and toxicology in animals and humans Addiction May 1, 1994
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and 21 more in the library