PMID- 19965941
OWN - NLM
STAT- MEDLINE
DCOM- 20100426
LR  - 20131121
IS  - 1461-7285 (Electronic)
IS  - 0269-8811 (Linking)
VI  - 24
IP  - 2
DP  - 2010 Feb
TI  - Effect of acute brain tyrosine depletion on MDMA-induced changes in brain 5-HT.
PG  - 267-74
LID - 10.1177/0269881109348163 [doi]
AB  - The mechanism by which 3,4-methylenedioxymethamphetamine (MDMA) produces 
      5-hydroxytryptamine (5-HT, serotonin) neurotoxicity has been suggested to involve 
      an acute release of tyrosine and its non-enzymatic conversion to dopamine. To 
      determine whether brain tyrosine availability is important in MDMA-induced 
      neurotoxicity, brain tyrosine was acutely depleted with a tyrosine-free amino 
      acid mixture (1 g/kg intraperitoneal; twice 1 h apart) which was administered 
      prior to an injection of MDMA (12.5 mg/kg intraperitoneal). A small increase in 
      both the hippocampal and striatal tyrosine concentration occurred in control rats 
      treated with MDMA. The tyrosine-free amino acid mixture significantly decreased 
      tyrosine levels by more than 50% in both brain regions 2 h after injection of 
      either MDMA or saline. MDMA significantly reduced brain 5-HT content 2 h later, 
      but this was of a similar magnitude in control and tyrosine-depleted groups. The 
      long-term neurotoxic 5-HT loss in the hippocampus induced two weeks after MDMA 
      administration was unaltered by the tyrosine-free amino acid mixture. Striatal 
      dopamine content was unaffected by acute MDMA in all groups, while the 
      tyrosine-free amino acid mixture given with MDMA significantly decreased striatal 
      dopamine content 2 weeks later. The tyrosine-free amino acid mixture given alone 
      had no affect on rectal body temperature but attenuated the duration of 
      MDMA-induced hyperthermia. The results confirmed the ability of systemic MDMA to 
      acutely increase brain tyrosine content, but also indicated that a marked acute 
      reduction of brain tyrosine does not directly affect either immediate 5-HT 
      release (as measured by tissue depletion) or long-term hippocampal serotonergic 
      neurotoxicity produced by MDMA.
FAU - Rodsiri, R
AU  - Rodsiri R
AD  - School of Biomedical Sciences, Institute of Neuroscience, University of 
      Nottingham, Nottingham, UK.
FAU - Green, A R
AU  - Green AR
FAU - Marsden, C A
AU  - Marsden CA
FAU - Fone, K C F
AU  - Fone KC
LA  - eng
PT  - Journal Article
DEP - 20091204
PL  - United States
TA  - J Psychopharmacol
JT  - Journal of psychopharmacology (Oxford, England)
JID - 8907828
RN  - 0 (Serotonin Agents)
RN  - 333DO1RDJY (Serotonin)
RN  - 42HK56048U (Tyrosine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Corpus Striatum/drug effects/metabolism
MH  - Dopamine/metabolism
MH  - Fever/chemically induced
MH  - Hippocampus/drug effects/metabolism
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Neurotoxicity Syndromes/*etiology
MH  - Rats
MH  - Serotonin/*metabolism
MH  - Serotonin Agents/toxicity
MH  - Time Factors
MH  - Tyrosine/deficiency/*metabolism
EDAT- 2009/12/08 06:00
MHDA- 2010/04/27 06:00
CRDT- 2009/12/08 06:00
PHST- 2009/12/08 06:00 [entrez]
PHST- 2009/12/08 06:00 [pubmed]
PHST- 2010/04/27 06:00 [medline]
AID - 0269881109348163 [pii]
AID - 10.1177/0269881109348163 [doi]
PST - ppublish
SO  - J Psychopharmacol. 2010 Feb;24(2):267-74. doi: 10.1177/0269881109348163. Epub 
      2009 Dec 4.