PMID- 17047928
OWN - NLM
STAT- MEDLINE
DCOM- 20070302
LR  - 20181113
IS  - 0033-3158 (Print)
IS  - 0033-3158 (Linking)
VI  - 189
IP  - 4
DP  - 2007 Jan
TI  - Binge ethanol administration enhances the MDMA-induced long-term 5-HT 
      neurotoxicity in rat brain.
PG  - 459-70
AB  - RATIONALE: Ecstasy abuse commonly occurs in hot, overcrowded environments in 
      combination with alcohol. Around 90% of ecstasy users take ethanol; over 70% of 
      these users also often drink alcohol at hazardous levels. OBJECTIVES: We wished 
      to examine whether binge ethanol administration enhanced the long-lasting 5-HT 
      neurotoxicity induced by 3,4-methylenedioxymethamphetamine (MDMA) in rats 
      maintained at high ambient temperature and the role of acetaldehyde. MATERIALS 
      AND METHODS: Rats were treated with a 4-day ethanol regimen leading to plasma 
      ethanol levels of around 450 mg/dl. On day 5, rats were placed at 30 degrees C 
      and administered MDMA (5 mg/kg). Rectal temperature and hydroxyl radical 
      formation were measured immediately before and up to 6 h after MDMA. 5-HT 
      concentration and 5-HT transporter density were determined 7 days later. A group 
      of rats received cyanamide (50 mg/kg) on days 1 and 3 of the 4-day-ethanol 
      inhalation. RESULTS: In ethanol treated rats, MDMA produced a hyperthermic 
      response similar to that observed in controls but enhanced the loss of 5-HT 
      concentration and 5-HT transporter density in the hippocampus. Cyanamide elevated 
      the plasma acetaldehyde concentration fivefold to sevenfold, reduced the 
      MDMA-induced hyperthermia and increased the neuronal damage with neurotoxicity 
      also appearing in the cortex. MDMA increased hydroxyl radical production in the 
      hippocampus, the effect being more marked in rats pre-exposed to ethanol. 
      CONCLUSIONS: Binge ethanol administration enhances the MDMA-induced long-term 
      5-HT neurotoxicity by a mechanism not related to changes in acute hyperthermia 
      but probably involving hydroxyl radical formation. The magnitude of this effect 
      is more pronounced after increasing plasma acetaldehyde levels by aldehyde 
      dehydrogenase inhibition.
FAU - Izco, Maria
AU  - Izco M
AD  - Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, 
      Madrid, 28040, Spain.
FAU - Orio, Laura
AU  - Orio L
FAU - O'Shea, Esther
AU  - O'Shea E
FAU - Colado, M Isabel
AU  - Colado MI
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20061018
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Central Nervous System Depressants)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Serotonin Agents)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 333DO1RDJY (Serotonin)
RN  - 3352-57-6 (Hydroxyl Radical)
RN  - 3K9958V90M (Ethanol)
RN  - 420-04-2 (Cyanamide)
RN  - EC 1.2.1.3 (Aldehyde Dehydrogenase)
RN  - GO1N1ZPR3B (Acetaldehyde)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
CIN - Psychopharmacology (Berl). 2007 Mar;190(4):581-2. PMID: 17235607
CIN - Psychopharmacology (Berl). 2007 Apr;191(2):387-8. PMID: 17265072
MH  - Acetaldehyde/metabolism
MH  - Alcoholic Intoxication/complications
MH  - Aldehyde Dehydrogenase/antagonists & inhibitors
MH  - Animals
MH  - Body Temperature/drug effects
MH  - Brain/*drug effects/metabolism
MH  - Central Nervous System Depressants/administration & dosage/*adverse 
      effects/blood/metabolism
MH  - Cyanamide/pharmacology
MH  - Drug Interactions
MH  - Enzyme Inhibitors/pharmacology
MH  - Ethanol/administration & dosage/*adverse effects/blood/metabolism
MH  - Fever/chemically induced/metabolism
MH  - *Hot Temperature
MH  - Hydroxyl Radical/metabolism
MH  - Inhalation Exposure
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Neurotoxicity Syndromes/complications/*metabolism/physiopathology
MH  - Rats
MH  - Serotonin/*metabolism
MH  - Serotonin Agents/*toxicity
MH  - Serotonin Plasma Membrane Transport Proteins/metabolism
MH  - Serotonin Syndrome/metabolism
MH  - Time Factors
EDAT- 2006/10/19 09:00
MHDA- 2007/03/03 09:00
CRDT- 2006/10/19 09:00
PHST- 2006/06/16 00:00 [received]
PHST- 2006/09/26 00:00 [accepted]
PHST- 2006/10/19 09:00 [pubmed]
PHST- 2007/03/03 09:00 [medline]
PHST- 2006/10/19 09:00 [entrez]
AID - 10.1007/s00213-006-0602-1 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2007 Jan;189(4):459-70. doi: 
      10.1007/s00213-006-0602-1. Epub 2006 Oct 18.