PMID- 16399699
OWN - NLM
STAT- MEDLINE
DCOM- 20060331
LR  - 20200225
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 26
IP  - 1
DP  - 2006 Jan 4
TI  - L-tyrosine contributes to (+)-3,4-methylenedioxymethamphetamine-induced serotonin 
      depletions.
PG  - 290-9
AB  - The specific mechanisms underlying (+)-3,4-methylenedioxymethamphetamine 
      (MDMA)-induced damage to 5-HT terminals are unknown. Despite the hypothesized 
      role for dopamine (DA) and DA-derived free radicals in mediating this damage, it 
      remains unclear why MDMA produces long-term depletions of 5-HT in brain regions 
      that are sparsely innervated by DA neurons. We hypothesized that the precursor to 
      DA biosynthesis, tyrosine, mediates MDMA-induced 5-HT depletions. Extracellular 
      tyrosine concentrations increased fivefold in striatum and 2.5-fold in 
      hippocampus during the administration of neurotoxic doses of MDMA. In vitro 
      results show that L-tyrosine can be hydroxylated nonenzymatically to the DA 
      precursor l-3,4-dihydroxyphenylalanine (DOPA) under pro-oxidant conditions. The 
      local infusion of L-tyrosine into the striatum or hippocampus during MDMA 
      administration potentiated the acute increase in extracellular DA and the 
      long-term depletion of 5-HT after MDMA. Coinfusion of the aromatic amino acid 
      decarboxylase (AADC) inhibitor m-hydroxybenzylhydrazine attenuated these effects 
      in hippocampus and decreased basal extracellular DA in the striatum. In contrast, 
      the reverse dialysis of the tyrosine hydroxylase inhibitor 
      alpha-methyl-p-tyrosine into the hippocampus did not affect MDMA-induced 
      increases in extracellular DA or the long-term depletion in 5-HT. These results 
      show that MDMA increases the concentration of tyrosine in the brain to cause a 
      long-term depletion of 5-HT via the nonenzymatic, tyrosine 
      hydroxylase-independent, hydroxylation of tyrosine to DOPA and subsequently to DA 
      via AADC. Overall, the findings suggest that MDMA depletes 5-HT by increasing 
      tyrosine and its eventual conversion to DA within 5-HT terminals.
FAU - Breier, Joseph M
AU  - Breier JM
AD  - Department of Pharmacology and Experimental Therapeutics, Boston University 
      School of Medicine, Boston, Massachusetts 02118, USA.
FAU - Bankson, Michael G
AU  - Bankson MG
FAU - Yamamoto, Bryan K
AU  - Yamamoto BK
LA  - eng
GR  - DA19486/DA/NIDA NIH HHS/United States
GR  - F31 DA016486/DA/NIDA NIH HHS/United States
GR  - DA16866/DA/NIDA NIH HHS/United States
GR  - R01 DA016866/DA/NIDA NIH HHS/United States
GR  - R01 DA019486/DA/NIDA NIH HHS/United States
GR  - DA16486/DA/NIDA NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Serotonin Antagonists)
RN  - 333DO1RDJY (Serotonin)
RN  - 42HK56048U (Tyrosine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Corpus Striatum/drug effects/metabolism
MH  - Drug Synergism
MH  - Injections, Intraventricular
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*administration & dosage
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin/*metabolism
MH  - Serotonin Antagonists/*administration & dosage
MH  - Tyrosine/*administration & dosage/*physiology
PMC - PMC6674330
EDAT- 2006/01/10 09:00
MHDA- 2006/04/01 09:00
PMCR- 2006/07/04
CRDT- 2006/01/10 09:00
PHST- 2006/01/10 09:00 [pubmed]
PHST- 2006/04/01 09:00 [medline]
PHST- 2006/01/10 09:00 [entrez]
PHST- 2006/07/04 00:00 [pmc-release]
AID - 26/1/290 [pii]
AID - 10.1523/JNEUROSCI.3353-05.2006 [doi]
PST - ppublish
SO  - J Neurosci. 2006 Jan 4;26(1):290-9. doi: 10.1523/JNEUROSCI.3353-05.2006.