PMID- 18074122
OWN - NLM
STAT- MEDLINE
DCOM- 20080903
LR  - 20211020
IS  - 0033-3158 (Print)
IS  - 0033-3158 (Linking)
VI  - 197
IP  - 2
DP  - 2008 Apr
TI  - The relationship between core body temperature and 
      3,4-methylenedioxymethamphetamine metabolism in rats: implications for 
      neurotoxicity.
PG  - 263-78
AB  - RATIONALE: A close relationship appears to exist between 
      3,4-methylenedioxymethamphetamine (MDMA)-induced changes in core body temperature 
      and long-term serotonin (5-HT) loss. OBJECTIVE: We investigated whether changes 
      in core body temperature affect MDMA metabolism. MATERIALS AND METHODS: Male 
      Wistar rats were treated with MDMA at ambient temperatures of 15, 21.5, or 30 
      degrees C to prevent or exacerbate MDMA-induced hyperthermia. Plasma 
      concentrations of MDMA and its main metabolites were determined for 6 h. Seven 
      days later, animals were killed and brain indole content was measured. RESULTS: 
      The administration of MDMA at 15 degrees C blocked the hyperthermic response and 
      long-term 5-HT depletion found in rats treated at 21.5 degrees C. At 15 degrees 
      C, plasma concentrations of MDMA were significantly increased, whereas those of 
      three of its main metabolites were reduced when compared to rats treated at 21.5 
      degrees C. By contrast, hyperthermia and indole deficits were exacerbated in rats 
      treated at 30 degrees C. Noteworthy, plasma concentrations of MDMA metabolites 
      were greatly enhanced in these animals. Instrastriatal perfusion of MDMA (100 
      microM for 5 h at 21 degrees C) did not potentiate the long-term depletion of 
      5-HT after systemic MDMA. Furthermore, interfering in MDMA metabolism using the 
      catechol-O-methyltransferase inhibitor entacapone potentiated the neurotoxicity 
      of MDMA, indicating that metabolites that are substrates for this enzyme may 
      contribute to neurotoxicity. CONCLUSIONS: This is the first report showing a 
      direct relationship between core body temperature and MDMA metabolism. This 
      finding has implications on both the temperature dependence of the mechanism of 
      MDMA neurotoxicity and human use, as hyperthermia is often associated with MDMA 
      use in humans.
FAU - Goni-Allo, Beatriz
AU  - Goni-Allo B
AD  - Department of Pharmacology, School of Medicine, University of Navarra, c/ 
      Irunlarrea 1, 31008 Pamplona, Spain.
FAU - O Mathuna, Brian
AU  - O Mathuna B
FAU - Segura, Mireia
AU  - Segura M
FAU - Puerta, Elena
AU  - Puerta E
FAU - Lasheras, Berta
AU  - Lasheras B
FAU - de la Torre, Rafael
AU  - de la Torre R
FAU - Aguirre, Norberto
AU  - Aguirre N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071212
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Catechol O-Methyltransferase Inhibitors)
RN  - 0 (Catechols)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hallucinogens)
RN  - 0 (Nitriles)
RN  - 333DO1RDJY (Serotonin)
RN  - 42HK56048U (Tyrosine)
RN  - 4975G9NM6T (entacapone)
RN  - 54-16-0 (Hydroxyindoleacetic Acid)
RN  - EC 2.1.1.6 (Catechol O-Methyltransferase)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
CIN - Psychopharmacology (Berl). 2009 Jun;204(2):375-8. PMID: 19139850
MH  - Animals
MH  - Body Temperature/drug effects/*physiology
MH  - Brain Chemistry/drug effects
MH  - Catechol O-Methyltransferase/metabolism
MH  - Catechol O-Methyltransferase Inhibitors
MH  - Catechols/pharmacology
MH  - Data Interpretation, Statistical
MH  - Drug Synergism
MH  - Enzyme Inhibitors/pharmacology
MH  - Fever/chemically induced
MH  - Hallucinogens/*metabolism/*toxicity
MH  - Hydroxyindoleacetic Acid/metabolism
MH  - Male
MH  - Microdialysis
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*metabolism/*toxicity
MH  - Neurotoxicity Syndromes/*psychology
MH  - Nitriles/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Serotonin/metabolism
MH  - Tyrosine/blood
EDAT- 2007/12/13 09:00
MHDA- 2008/09/04 09:00
CRDT- 2007/12/13 09:00
PHST- 2007/07/04 00:00 [received]
PHST- 2007/11/20 00:00 [accepted]
PHST- 2007/12/13 09:00 [pubmed]
PHST- 2008/09/04 09:00 [medline]
PHST- 2007/12/13 09:00 [entrez]
AID - 10.1007/s00213-007-1027-1 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2008 Apr;197(2):263-78. doi: 
      10.1007/s00213-007-1027-1. Epub 2007 Dec 12.