The Acute Toxic and Neurotoxic Effects of 3,4-methylenedioxymethamphetamine are More Pronounced in Adolescent than Adult Mice
N. Chitre, M. Bagwell, K. Murnane
Behavioural Brain Research December 3, 2019 DOI: 10.1016/j.bbr.2019.112413 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study in rodents Peer reviewed |
|---|---|
| Population | Male Swiss-Webster mice; adolescents 6-7 weeks of age and adults 16-18 weeks of age |
| Intervention | MDMA |
| Dose | 20 mg/kg, 4 administrations spaced every 2 hours |
| Measures | high-pressure liquid chromatography (HPLC) coupled to electrochemical detection |
| Topics | MDMA |
| Key findings | Binge MDMA (20 mg/kg, four doses two hours apart) produced greater acute lethality, hyperthermia, body-weight loss, and striatal dopamine loss in adolescent mice than in adult mice. Adolescents also showed increased dopamine turnover to DOPAC, which adults did not, suggesting adolescents may be more vulnerable to MDMA toxicity or adults more protected; the authors caution that MDMA's therapeutic window may differ between adolescents and mature adults. |
Abstract
3,4-methylenedioxymethamphetamine (MDMA) recently achieved breakthrough status from the Food and Drug Administration (FDA) for post-traumatic stress disorder (PTSD). However, evidence indicates that exposure to toxic doses of 3,4-methylenedioxymethamphetamine (MDMA) can lead to long-lasting dysregulation of brain monoaminergic neurotransmitters, primarily from studies conducted in young adult rodents. To date, there is a paucity of data on whether toxic doses of MDMA can differentially affect neurotransmitter systems in adolescents and mature adults, which is an important question as adolescents and adults may be differentially vulnerable to MDMA abuse. In the current study, adolescent (6–7 weeks of age) and adult (16–18 weeks of age) male, Swiss-Webster mice were exposed to MDMA (20 mg/kg) using a binge-like dosing regimen (4 administrations spaced every 2 hours). Acute lethality, acute hyperthermia, and acute decreases in body weight effects following MDMA administration were more pronounced in adolescent than adult mice. Likewise, acute loss of striatal dopamine neurochemistry was also exacerbated in adolescents, as determined by high-pressure liquid chromatography (HPLC) coupled to electrochemical detection. Exposure to MDMA induced greater turnover of dopamine into its major metabolite dihydroxyphenylacetic acid (DOPAC) in adolescents, but not in adults, suggesting a novel mechanism through which adolescents may show increased vulnerability to the acute toxic and neurotoxic effects of MDMA, or conversely that mature adults show greater protection. These data caution that MDMA exposure in adolescence may be particularly dangerous and that the therapeutic window for MDMA may differ between adolescents and mature adults.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.