The combined effects of 3,4-methylenedioxymethamphetamine (MDMA) and selected substituted methcathinones on measures of neurotoxicity
N. Miner, J. O'Callaghan, T. Phillips, Aaron Janowsky
Neurotoxicology and Teratology February 16, 2017 DOI: 10.1016/j.ntt.2017.02.003 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment Peer reviewed |
|---|---|
| Population | C57BL/6J mice |
| Interventions | MDMA methylone MDPV |
| Dose | MDMA 15 or 30 mg/kg, methylone 20 mg/kg, MDPV 1 mg/kg, methylone/MDMA 20/15 mg/kg, MDPV/MDMA 1/15 mg/kg |
| Duration | 2 or 7 days |
| Topics | MDMA |
| Citations | 25 |
| Key findings | Combined administration of methylone or MDPV with MDMA blocked the astrocyte activation caused by MDMA alone, and MDPV modulated thermoregulation through a distinct mechanism. |
Abstract
The rise in popularity of substituted methcathinones (aka “bath salts”) has increased the focus on their neurotoxic effects. Two commonly abused methcathinones, 3,4-methylenedioxymethcathinone (methylone, MDMC) and 3,4-methylenedioxypyrovalerone (MDPV), are often concomitantly ingested with the illicit drug 3,4-methylenedioxymethamphetamine (MDMA). To examine potential neurotoxic effects of these drug combinations, C57BL/6J mice were administered 4 i.p. injection of the drugs, at 2 h intervals, either singularly: MDMA 15 or 30 mg/kg, methylone 20 mg/kg, MDPV 1 mg/kg; or in combination: methylone/MDMA 20/15 mg/kg, MDPV/MDMA 1/15 mg/kg. Drug effects on thermoregulation were characterized and striatal tissue analyzed after 2 or 7 days for dopamine (DA) and tyrosine hydroxylase (TH) levels, as well as glial fibrillary acidic protein (GFAP) expression. Two days following drug administration, DA and TH were decreased only in the MDMA 30 mg/kg group, whereas GFAP expression was dose-dependently increased by MDMA alone. While the combination of the methcathinones with the lower MDMA dose did not affect DA or TH levels, both blocked the MDMA-induced increase in GFAP expression. Seven days following drug administration, there were no significant differences in DA, TH, or GFAP for any treatment group, indicating that changes in DA, TH, and GFAP were transient. Five of the six drug groups exhibited acute hypothermia followed by gradually increasing temperatures. Animals treated with MDPV did not exhibit these biphasic temperature changes, and resembled the saline group. These results indicate that specific effects of both methylone and MDPV on DA depletion or astrocyte activation in the striatum are not additive with effects of MDMA, but block astrogliosis caused by MDMA alone. Additionally, MDPV modulates thermoregulation through a different mechanism than methylone or MDMA.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 4
- Brain dysfunctions and neurotoxicity induced by psychostimulants in experimental models and humans: an overview of recent findings Neural Regeneration Research February 22, 2024
- High ambient temperature increases the toxicity and lethality of 3,4-methylenedioxymethamphetamine and methcathinone. Pharmacology, Biochemistry, and Behavior May 2020
- Synthetic psychoactive cathinones: hypothermia and reduced lethality compared to methamphetamine and methylenedioxymethamphetamine. Pharmacology, Biochemistry, and Behavior April 2020
- The Acute Toxic and Neurotoxic Effects of 3,4-methylenedioxymethamphetamine are More Pronounced in Adolescent than Adult Mice Behavioural Brain Research December 3, 2019
Cites 14
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and 9 more in the library