PMID- 9621349
OWN - NLM
STAT- MEDLINE
DCOM- 19980902
LR  - 20191210
IS  - 0161-813X (Print)
IS  - 0161-813X (Linking)
VI  - 19
IP  - 3
DP  - 1998 Jun
TI  - An integrated hypothesis for the serotonergic axonal loss induced by 
      3,4-methylenedioxymethamphetamine.
PG  - 427-41
AB  - Administration of the street drug 3,4-methylenedioxymethamphetamine (MDMA) to 
      various experimental animals has been shown in several laboratories to induce 
      selective damage to serotonergic axons and axon terminals. This review examines 
      the current available evidence supporting the development of serotonin (5-HT) 
      neurotoxicity in animals and humans. There are a plethora of hypotheses that 
      attempt to explain the mechanisms involved in the development of this 
      serotonergic neurotoxicity. An integrated hypothesis incorporating most of the 
      speculated neurotransmitters theorized to be involved in the process is proposed. 
      This hypothesis states that MDMA induces the following sequence of events 
      resulting in the serotonergic neurotoxicity: 1. MDMA induces an acute release of 
      5-HT and dopamine (DA). 2. This acute release is followed by depletion of 
      intraneuronal 5-HT stores. 3. The initially released 5-HT activates post-synaptic 
      5-HT2A/2C receptors located on GABA interneurons resulting in a decrease in 
      GABAegic transmission and increased DA release and synthesis. 4. The excessive DA 
      released then may be transported into the depleted 5-HT terminal. 5. The DA is 
      then deaminated by monoamine oxidase B (MAO-B) located within the 5-HT terminal. 
      This results in free-radical formation and the selective degeneration of the 
      serotonergic axons and axon terminals. While there is no clear evidence that 
      human users of the drug are suffering a similar neurotoxicity, data are presented 
      suggesting that there remains cause for concern.
FAU - Sprague, J E
AU  - Sprague JE
AD  - Department of Pharmaceutical and Biomedical Sciences, Ohio Northern University, 
      Ada 45810, USA.
FAU - Everman, S L
AU  - Everman SL
FAU - Nichols, D E
AU  - Nichols DE
LA  - eng
GR  - DA 04758/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - Netherlands
TA  - Neurotoxicology
JT  - Neurotoxicology
JID - 7905589
RN  - 0 (Illicit Drugs)
RN  - 0 (Neurotoxins)
RN  - 0 (Neurotransmitter Agents)
RN  - 0 (Serotonin Agents)
RN  - 333DO1RDJY (Serotonin)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Axons/*drug effects
MH  - Humans
MH  - Illicit Drugs/*toxicity
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Neurotoxins/*toxicity
MH  - Neurotransmitter Agents/metabolism
MH  - Serotonin/*physiology
MH  - Serotonin Agents/*toxicity
MH  - gamma-Aminobutyric Acid/physiology
RF  - 113
EDAT- 1998/06/11 00:00
MHDA- 1998/06/11 00:01
CRDT- 1998/06/11 00:00
PHST- 1998/06/11 00:00 [pubmed]
PHST- 1998/06/11 00:01 [medline]
PHST- 1998/06/11 00:00 [entrez]
PST - ppublish
SO  - Neurotoxicology. 1998 Jun;19(3):427-41.