PMID- 23892197
OWN - NLM
STAT- MEDLINE
DCOM- 20140415
LR  - 20211021
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Print)
IS  - 0024-3205 (Linking)
VI  - 97
IP  - 1
DP  - 2014 Feb 27
TI  - Effects of combined treatment with mephedrone and methamphetamine or 
      3,4-methylenedioxymethamphetamine on serotonin nerve endings of the hippocampus.
PG  - 31-6
LID - S0024-3205(13)00402-5 [pii]
LID - 10.1016/j.lfs.2013.07.015 [doi]
AB  - AIMS: Mephedrone is a stimulant drug of abuse with close structural and 
      mechanistic similarities to methamphetamine and 3,4-methylenedioxymethamphetamine 
      (MDMA). Although mephedrone does not damage dopamine nerve endings it increases 
      the neurotoxicity of amphetamine, methamphetamine and MDMA. The effects of 
      mephedrone on serotonin (5HT) nerve endings are not fully understood, with some 
      investigators reporting damage while others conclude it does not. Presently, we 
      investigate if mephedrone given alone or with methamphetamine or MDMA damages 5HT 
      nerve endings of the hippocampus. MAIN METHODS: The status of 5HT nerve endings 
      in the hippocampus of female C57BL mice was assessed through measures of 5HT by 
      HPLC and by immunoblot analysis of serotonin transporter (SERT) and tryptophan 
      hydroxylase 2 (TPH2), selective markers of 5HT nerve endings. Astrocytosis was 
      assessed through measures of glial fibrillary acidic protein (GFAP) 
      (immunoblotting) and microglial activation was determined by histochemical 
      staining with Isolectin B4. KEY FINDINGS: Mephedrone alone did not cause 
      persistent reductions in the levels of 5HT, SERT or TPH2. Methamphetamine and 
      MDMA alone caused mild reductions in 5HT but did not change SERT and TPH2 levels. 
      Combined treatment with mephedrone and methamphetamine or MDMA did not change the 
      status of 5HT nerve endings to an extent that was different from either drug 
      alone. SIGNIFICANCE: Mephedrone does not cause toxicity to 5HT nerve endings of 
      the hippocampus. When co-administered with methamphetamine or MDMA, drugs that 
      are often co-abused with mephedrone by humans, toxicity is not increased as is 
      the case for dopamine nerve endings when these drugs are taken together.
CI  - (c) 2013.
FAU - Angoa-Perez, Mariana
AU  - Angoa-Perez M
AD  - Research & Development Service, John D. Dingell VA Medical Center, Detroit, MI 
      48201, USA; Department of Psychiatry & Behavioral Neurosciences, Wayne State 
      University School of Medicine, Detroit, MI 48201, USA.
FAU - Kane, Michael J
AU  - Kane MJ
AD  - Research & Development Service, John D. Dingell VA Medical Center, Detroit, MI 
      48201, USA; Department of Psychiatry & Behavioral Neurosciences, Wayne State 
      University School of Medicine, Detroit, MI 48201, USA.
FAU - Herrera-Mundo, Nieves
AU  - Herrera-Mundo N
AD  - Research & Development Service, John D. Dingell VA Medical Center, Detroit, MI 
      48201, USA; Department of Psychiatry & Behavioral Neurosciences, Wayne State 
      University School of Medicine, Detroit, MI 48201, USA.
FAU - Francescutti, Dina M
AU  - Francescutti DM
AD  - Research & Development Service, John D. Dingell VA Medical Center, Detroit, MI 
      48201, USA; Department of Psychiatry & Behavioral Neurosciences, Wayne State 
      University School of Medicine, Detroit, MI 48201, USA.
FAU - Kuhn, Donald M
AU  - Kuhn DM
AD  - Research & Development Service, John D. Dingell VA Medical Center, Detroit, MI 
      48201, USA; Department of Psychiatry & Behavioral Neurosciences, Wayne State 
      University School of Medicine, Detroit, MI 48201, USA. Electronic address: 
      donald.kuhn@wayne.edu.
LA  - eng
GR  - I01 RX000458/RX/RRD VA/United States
GR  - R01 DA010756/DA/NIDA NIH HHS/United States
GR  - R21 DA039667/DA/NIDA NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20130724
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Designer Drugs)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 333DO1RDJY (Serotonin)
RN  - 44RAL3456C (Methamphetamine)
RN  - 8BA8T27317 (mephedrone)
RN  - EC 1.14.16.4 (Tph2 protein, mouse)
RN  - EC 1.14.16.4 (Tryptophan Hydroxylase)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Central Nervous System Stimulants/administration & dosage/toxicity
MH  - Chromatography, High Pressure Liquid
MH  - Designer Drugs/administration & dosage/toxicity
MH  - Female
MH  - Hippocampus/*drug effects/metabolism
MH  - Methamphetamine/administration & dosage/*analogs & derivatives/*toxicity
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage/*toxicity
MH  - Nerve Endings/*drug effects/metabolism
MH  - Neurotoxicity Syndromes/etiology
MH  - Serotonin/metabolism
MH  - Serotonin Plasma Membrane Transport Proteins/drug effects/metabolism
MH  - Tryptophan Hydroxylase/metabolism
PMC - PMC3858458
MID - NIHMS509182
OTO - NOTNLM
OT  - Bath salts
OT  - MDMA
OT  - Mephedrone
OT  - Methamphetamine
OT  - Neurotoxicity
OT  - Serotonin
COIS- Conflict of interest statement All the authors declared no competing interests.
EDAT- 2013/07/31 06:00
MHDA- 2014/04/16 06:00
PMCR- 2015/02/27
CRDT- 2013/07/30 06:00
PHST- 2013/05/14 00:00 [received]
PHST- 2013/07/05 00:00 [revised]
PHST- 2013/07/11 00:00 [accepted]
PHST- 2013/07/30 06:00 [entrez]
PHST- 2013/07/31 06:00 [pubmed]
PHST- 2014/04/16 06:00 [medline]
PHST- 2015/02/27 00:00 [pmc-release]
AID - S0024-3205(13)00402-5 [pii]
AID - 10.1016/j.lfs.2013.07.015 [doi]
PST - ppublish
SO  - Life Sci. 2014 Feb 27;97(1):31-6. doi: 10.1016/j.lfs.2013.07.015. Epub 2013 Jul 
      24.