PMID- 28212938 OWN - NLM STAT- MEDLINE DCOM- 20180321 LR - 20240213 IS - 1872-9738 (Electronic) IS - 0892-0362 (Print) IS - 0892-0362 (Linking) VI - 61 DP - 2017 May TI - The combined effects of 3,4-methylenedioxymethamphetamine (MDMA) and selected substituted methcathinones on measures of neurotoxicity. PG - 74-81 LID - S0892-0362(16)30134-9 [pii] LID - 10.1016/j.ntt.2017.02.003 [doi] AB - 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 2h intervals, either singularly: MDMA 15 or 30mg/kg, methylone 20mg/kg, MDPV 1mg/kg; or in combination: methylone/MDMA 20/15mg/kg, MDPV/MDMA 1/15mg/kg. Drug effects on thermoregulation were characterized and striatal tissue analyzed after 2 or 7days 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 30mg/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. CI - Published by Elsevier Inc. FAU - Miner, Nicholas B AU - Miner NB AD - Research Service, VA Portland Health Care System, Portland, OR, USA; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA. FAU - O'Callaghan, James P AU - O'Callaghan JP AD - Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Morgantown, WV, USA. FAU - Phillips, Tamara J AU - Phillips TJ AD - Research Service, VA Portland Health Care System, Portland, OR, USA; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA; The Methamphetamine Abuse Research Center, Oregon Health & Science University, Portland, OR, USA. FAU - Janowsky, Aaron AU - Janowsky A AD - Research Service, VA Portland Health Care System, Portland, OR, USA; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA; The Methamphetamine Abuse Research Center, Oregon Health & Science University, Portland, OR, USA; Department of Psychiatry, Oregon Health & Science University, Portland, OR, USA. Electronic address: janowsky@ohsu.edu. LA - eng GR - T32 DA007262/DA/NIDA NIH HHS/United States GR - Y01 DA005007/DA/NIDA NIH HHS/United States GR - U01 DA041579/DA/NIDA NIH HHS/United States GR - P50 DA018165/DA/NIDA NIH HHS/United States GR - I01 BX002758/BX/BLRD VA/United States GR - I01 BX002106/BX/BLRD VA/United States GR - T32 NS007466/NS/NINDS NIH HHS/United States PT - Journal Article DEP - 20170216 PL - United States TA - Neurotoxicol Teratol JT - Neurotoxicology and teratology JID - 8709538 RN - 0 (Benzodioxoles) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Pyrrolidines) RN - 44RAL3456C (Methamphetamine) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - L4I4B1R01F (methylone) RN - VTD58H1Z2X (Dopamine) RN - 0 (Synthetic Cathinone) SB - IM MH - Animals MH - Benzodioxoles/*toxicity MH - Body Temperature Regulation/*drug effects MH - Corpus Striatum/metabolism MH - Dopamine/metabolism MH - Glial Fibrillary Acidic Protein/metabolism MH - Gliosis/chemically induced MH - Male MH - Methamphetamine/*analogs & derivatives/toxicity MH - Mice MH - N-Methyl-3,4-methylenedioxyamphetamine/antagonists & inhibitors/*toxicity MH - Pyrrolidines/*toxicity MH - Tyrosine 3-Monooxygenase/*metabolism MH - Synthetic Cathinone PMC - PMC5453829 MID - NIHMS856283 OTO - NOTNLM OT - Dopamine OT - GFAP OT - MDMA OT - MDPV OT - Methylone OT - Neurotoxicity COIS- Disclosure The authors do not have any conflicts of interest to declare. EDAT- 2017/02/19 06:00 MHDA- 2018/03/22 06:00 PMCR- 2018/05/01 CRDT- 2017/02/19 06:00 PHST- 2016/11/10 00:00 [received] PHST- 2017/01/19 00:00 [revised] PHST- 2017/02/13 00:00 [accepted] PHST- 2017/02/19 06:00 [pubmed] PHST- 2018/03/22 06:00 [medline] PHST- 2017/02/19 06:00 [entrez] PHST- 2018/05/01 00:00 [pmc-release] AID - S0892-0362(16)30134-9 [pii] AID - 10.1016/j.ntt.2017.02.003 [doi] PST - ppublish SO - Neurotoxicol Teratol. 2017 May;61:74-81. doi: 10.1016/j.ntt.2017.02.003. Epub 2017 Feb 16.