PMID- 17629409
OWN - NLM
STAT- MEDLINE
DCOM- 20071214
LR  - 20150813
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 148
IP  - 1
DP  - 2007 Aug 10
TI  - Restoration of 3,4-methylenedioxymethamphetamine-induced 5-HT depletion by the 
      administration of L-5-hydroxytryptophan.
PG  - 212-20
AB  - BACKGROUND: 3,4-Methylenedioxymethamphetamine (MDMA) causes persistent decreases 
      in brain 5-HT content and 5-HT transporter (SERT) binding, with no detectable 
      changes in SERT protein. Such data suggest that MDMA impairs 5-HT transmission 
      but leaves 5-HT nerve terminals intact. To further test this hypothesis, we 
      carried out two types of experiments in rats exposed to high-dose MDMA. First, we 
      examined the effects of MDMA on SERT binding and function using different in 
      vitro assay conditions. Next, we treated rats with the 5-HT precursor, 
      l-5-hydroxytryptophan (5-HTP), in an attempt to restore MDMA-induced depletions 
      of 5-HT. METHODS: Rats received three i.p. injections of saline or MDMA (7.5 
      mg/kg), one injection every 2 h. Rats in one group were decapitated, and brain 
      tissue was assayed for SERT binding and [(3)H]5-HT uptake under conditions of 
      normal (100 or 126 mM) and low (20 mM) NaCl concentration. Rats from another 
      group received saline or 5-hydroxytryptophan/benserazide (5-HTP-B), each drug at 
      50 mg/kg i.p., and were killed 2 h later. RESULTS: MDMA reduced SERT binding to 
      10% of control when assayed in 100 mM NaCl, but this reduction was only 55% of 
      control in 20 mM NaCl. MDMA decreased immunoreactive 5-HT in caudate and 
      hippocampus to about 35% of control. Administration of 5-HTP-B to MDMA-pretreated 
      rats significantly increased the 5-HT signal toward normal levels in caudate (85% 
      of control) and hippocampus (66% of control). CONCLUSION: 1) Following high-dose 
      MDMA treatment sufficient to reduce SERT binding by 90%, a significant number of 
      functionally intact 5-HT nerve terminals survive. 2) The degree of MDMA-induced 
      decreases in SERT binding depends on the in vitro assay conditions. 3) 5-HTP-B 
      restores brain 5-HT depleted by MDMA, suggesting that this approach might be 
      clinically useful in abstinent MDMA users.
FAU - Wang, X
AU  - Wang X
AD  - Clinical Psychopharmacology Section, Intramural Research Program, National 
      Institute on Drug Abuse, National Institutes of Health, P.O. Box 5180, 5500 
      Nathan Shock Drive, Baltimore, MD 21224, USA.
FAU - Baumann, M H
AU  - Baumann MH
FAU - Dersch, C M
AU  - Dersch CM
FAU - Rothman, R B
AU  - Rothman RB
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20070712
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Antidepressive Agents, Second-Generation)
RN  - 0 (Hallucinogens)
RN  - 0 (Serotonin Agents)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 333DO1RDJY (Serotonin)
RN  - C1LJO185Q9 (5-Hydroxytryptophan)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - 5-Hydroxytryptophan/*pharmacology
MH  - Animals
MH  - Antidepressive Agents, Second-Generation/pharmacology
MH  - Binding, Competitive/drug effects/physiology
MH  - Brain/*drug effects/metabolism
MH  - Brain Chemistry/*drug effects/physiology
MH  - Cell Survival/drug effects/physiology
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions/physiology
MH  - Hallucinogens/antagonists & inhibitors/toxicity
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*antagonists & inhibitors/toxicity
MH  - Nerve Degeneration/chemically induced/drug therapy/physiopathology
MH  - Presynaptic Terminals/drug effects/metabolism
MH  - Radioligand Assay
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recovery of Function/drug effects/physiology
MH  - Serotonin/*deficiency
MH  - Serotonin Agents/pharmacology/toxicity
MH  - Serotonin Plasma Membrane Transport Proteins/drug effects/metabolism
MH  - Synaptic Transmission/drug effects/physiology
EDAT- 2007/07/17 09:00
MHDA- 2007/12/15 09:00
CRDT- 2007/07/17 09:00
PHST- 2007/04/02 00:00 [received]
PHST- 2007/05/21 00:00 [revised]
PHST- 2007/05/26 00:00 [accepted]
PHST- 2007/07/17 09:00 [pubmed]
PHST- 2007/12/15 09:00 [medline]
PHST- 2007/07/17 09:00 [entrez]
AID - S0306-4522(07)00673-2 [pii]
AID - 10.1016/j.neuroscience.2007.05.024 [doi]
PST - ppublish
SO  - Neuroscience. 2007 Aug 10;148(1):212-20. doi: 10.1016/j.neuroscience.2007.05.024. 
      Epub 2007 Jul 12.