Behavioral and neurochemical effects of repeated MDMA administration during late adolescence in the rat.
Brittney M Cox, Mrudang M Shah, Teri Cichon, Manuel E. Tancer, Matthew P. Galloway, David M Thomas, Shane A. Perrine
Progress in Neuro-Psychopharmacology and Biological Psychiatry January 3, 2014 DOI: 10.1016/j.pnpbp.2013.09.021 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experimental animal study Peer reviewed |
|---|---|
| Population | Late adolescent rats |
| Intervention | MDMA |
| Dose | 5 or 10 mg/kg |
| Duration | 4 twice-daily conditioning sessions; assessed 5 days after conditioning |
| Measures | open field test, light-dark box test, high-pressure liquid chromatography (HPLC) |
| Topics | Anxiety MDMA Serotonin |
| Keywords | 3,4-methylenedioxymethamphetamine 5-hiaa 5-HT Serotonin 5-hydroxyindoleacetic acid 5-hydroxytryptamine Anova Amygdala Conditioned place preference Dorsal raphe Hplc Ip Intraperitoneal Pnd Sem Sert Analysis of variance Postnatal date Serotonin transporter |
| Key findings | Repeated 10 mg/kg MDMA, but not 5 mg/kg, during late adolescence in rats produced conditioned place aversion and increased anxiety-like and avoidant behaviors during abstinence, alongside region-specific serotonin changes: decreased 5-HT in the dorsal raphe, increased 5-HT and 5-HIAA in the amygdala, and no change in the hippocampus. The authors suggest this region-specific serotonin dysregulation may contribute to maladaptive behavior. |
Abstract
Adolescents and young adults disproportionately abuse 3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy'); however, since most MDMA research has concentrated on adults, the effects of MDMA on the developing brain remain obscure. Therefore, we evaluated place conditioning to MDMA (or saline) during late adolescence and assessed anxiety-like behavior and monoamine levels during abstinence. Rats were conditioned to associate 5 or 10mg/kg MDMA or saline with contextual cues over 4 twice-daily sessions. Five days after conditioning, anxiety-like behavior was examined with the open field test and brain tissue was collected to assess serotonin (5-hydroxytryptamine, 5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the dorsal raphe, amygdala, and hippocampus by high-pressure liquid chromatography (HPLC). In a separate group of rats, anxiety-like and avoidant behaviors were measured using the light-dark box test under similar experimental conditions. MDMA conditioning caused a place aversion at 10, but not at 5, mg/kg, as well as increased anxiety-like behavior in the open field and avoidant behavior in light-dark box test at the same dose. Additionally, 10mg/kg MDMA decreased 5-HT in the dorsal raphe, increased 5-HT and 5-HIAA in the amygdala, and did not alter levels in the hippocampus. Overall, we show that repeated high (10mg/kg), but not low (5mg/kg), dose MDMA during late adolescence in rats increases anxiety-like and avoidant behaviors, accompanied by region-specific alterations in 5-HT levels during abstinence. These results suggest that MDMA causes a region-specific dysregulation of the serotonin system during adolescence that may contribute to maladaptive behavior.
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 12
- Neurotoxicity of MDMA: Main effects and mechanisms. Experimental Neurology October 1, 2021
- Use and abuse of dissociative and psychedelic drugs in adolescence Pharmacology, Biochemistry, and Behavior January 27, 2021
- Effects of acute social stress on the conditioned place preference induced by MDMA in adolescent and adult mice Behavioural Pharmacology September 1, 2014
- Increased iNOS and Nitrosative Stress in Dopaminergic Neurons of MDMA-Exposed Rats International Journal of Molecular Sciences March 12, 2019
- Longitudinal Examination of Learning and Memory in Rats Following Adolescent Exposure to 3,4-Methylenedioxymethamphetamine or 5-Methoxy-N,N-Diisopropyltryptamine Journal of Behavioral and Brain Science 2017
and 7 more in the library
Cites 22
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- Former chronic methylenedioxymethamphetamine (MDMA or ecstasy) users report mild depressive symptoms Journal of Psychopharmacology May 1, 2001
- Neuroanatomic specificity and time course of alterations in rat brain serotonergic pathways induced by MDMA (3,4‐methylenedioxymethamphetamine): Assessment using quantitative autoradiography Synapse August 1, 1991
- A developmental comparison of the neurobehavioral effects of ecstasy (MDMA) Neurotoxicology and Teratology October 21, 2006
- The Nature of 3, 4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonergic Dysfunction: Evidence for and Against the Neurodegeneration Hypothesis Current Neuropharmacology March 1, 2011
and 17 more in the library