The effects of ecstasy (MDMA) on brain serotonin transporters are dependent on age-of-first exposure in recreational users and animals.
Anne Klomp, Bjørnar den Hollander, Kora de Bruin, Jan Booij, Liesbeth Reneman
PLoS One 2012 DOI: 10.1371/journal.pone.0047524 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study in humans with parallel experimental study in rats Peer reviewed |
|---|---|
| Sample size | 33 |
| Population | Human ecstasy (MDMA) users stratified by age at first exposure (14-18 years vs 18-36 years), plus early-exposed adolescent and late-exposed adult rats |
| Intervention | Ecstasy (MDMA) |
| Duration | Assessed on average five years after first exposure |
| Measures | [(123)I]β-CIT single photon emission computed tomography (SERT density) |
| Topics | MDMA Serotonin |
| Key findings | Age at first ecstasy exposure predicted 79% of midbrain SERT variability in early-exposed users (first use at 14-18 years) but only 0.3% in late-exposed users (first use at 18-36 years), assessed about five years after first exposure; no such effect was seen in the frontal cortex. In rats, a significant age-by-treatment effect on SERT occurred only in the frontal cortex. The authors propose these differences reflect maturational stage of serotonin projection fields and serotonin's neurotrophic effects. |
Abstract
Little is known on the effects of ecstasy (MDMA, a potent 5-HT-releaser and neurotoxin) exposure on brain development in teenagers. The objective of this study was to investigate whether in humans, like previous observations made in animals, the effects of MDMA on the 5-HT system are dependent on age-of-first exposure. 5-HT transporter (SERT) densities in the frontal cortex and midbrain were assessed with [(123)I]β-CIT single photon emission computed tomography in 33 users of ecstasy. Subjects were stratified for early-exposed users (age-at-first exposure 14-18 years; developing brain), and late-exposed users (age-at-first exposure 18-36 years; mature brain). In parallel, we investigated the effects of age experimentally with MDMA in early-exposed (adolescent) rats and late-exposed (adult) rats using the same radioligand. On average, five years after first exposure, we found a strong inverse relationship, wherein age-at-first exposure predicted 79% of the midbrain SERT variability in early (developing brain) exposed ecstasy users, whereas this was only 0.3% in late (mature brain) exposed users (p=0.007). No such effect was observed in the frontal cortex. In rats, a significant age-BY-treatment effect (p<0.01) was observed as well, however only in the frontal cortex. These age-related effects most likely reflect differences in the maturational stage of the 5-HT projection fields at age-at-first exposure and enhanced outgrowth of the 5-HT system due to 5-HT's neurotrophic effects. Ultimately, our findings stress the need for more knowledge on the effects of pharmacotherapies that alter brain 5-HT levels in the pediatric population.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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- Are ecstasy induced serotonergic alterations overestimated for the majority of users? Journal of Psychopharmacology May 7, 2018
- 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
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