The combined effects of 3,4-methylenedioxymethamphetamine (MDMA) and selected substituted methcathinones on measures of neurotoxicity

Nicholas B. Miner, James P. O'Callaghan, Tamara Phillips, Aaron Janowsky

Research output: Contribution to journalArticle

13 Scopus citations

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.

Original languageEnglish (US)
JournalNeurotoxicology and Teratology
DOIs
StateAccepted/In press - Nov 10 2016

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Keywords

  • Dopamine
  • GFAP
  • MDMA
  • MDPV
  • Methylone
  • Neurotoxicity

ASJC Scopus subject areas

  • Toxicology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

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