PMID- 2457659
OWN - NLM
STAT- MEDLINE
DCOM- 19881007
LR  - 20191101
IS  - 0270-6474 (Print)
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Linking)
VI  - 8
IP  - 8
DP  - 1988 Aug
TI  - Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause 
      selective ablation of serotonergic axon terminals in forebrain: 
      immunocytochemical evidence for neurotoxicity.
PG  - 2788-803
AB  - The psychotropic amphetamine derivatives 3,4-methylenedioxyamphetamine (MDA) and 
      3,4-methylenedioxymethamphetamine (MDMA) have been used for recreational and 
      therapeutic purposes in man. In rats, these drugs cause large reductions in brain 
      levels of serotonin (5-HT). This study employs immunocytochemistry to 
      characterize the neurotoxic effects of these compounds upon monoaminergic neurons 
      in the rat brain. Two weeks after systemic administration of MDA or MDMA (20 
      mg/kg, s.c., twice daily for 4 d), there is profound loss of serotonergic (5-HT) 
      axons throughout the forebrain; catecholamine axons are completely spared. 
      Regional differences in drug toxicity are exemplified by partial sparing of 5-HT 
      axons in hippocampus, lateral hypothalamus, basal forebrain, and in some areas of 
      neocortex. The terminals of 5-HT axons are selectively ablated, while axons of 
      passage and raphe cell bodies are spared. Thickened preterminal fibers exhibit 
      increased staining due to damming-up of neurotransmitter and other axonal 
      constituents. Fine 5-HT axon terminals are extremely vulnerable to these drugs, 
      whereas terminal-like axons with large varicosities survive, raising the 
      possibility that some 5-HT axons may be resistant to the neurotoxic effects. At 
      short survivals, visualization of greatly swollen, fragmented 5-HT axons provides 
      anatomic evidence for degeneration of 5-HT projections. The results establish 
      that MDA and MDMA produce structural damage to 5-HT axon terminals followed by 
      lasting denervation of the forebrain. Both drugs have similar effects, but MDA 
      produces a greater reduction of 5-HT axons than does MDMA at the same dosage. The 
      selective degeneration of 5-HT axons indicates that these drugs may serve as 
      experimental tools to analyze the organization and function of 5-HT projections. 
      Caution should be exercised until further studies determine whether these 
      compounds may be hazardous in man.
FAU - O'Hearn, E
AU  - O'Hearn E
AD  - Department of Neuroscience, Johns Hopkins University School of Medicine, 
      Baltimore, Maryland 21205.
FAU - Battaglia, G
AU  - Battaglia G
FAU - De Souza, E B
AU  - De Souza EB
FAU - Kuhar, M J
AU  - Kuhar MJ
FAU - Molliver, M E
AU  - Molliver ME
LA  - eng
GR  - DA-04431/DA/NIDA NIH HHS/United States
GR  - NS-15199/NS/NINDS NIH HHS/United States
GR  - NS-21011/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Amphetamines)
RN  - 0 (Catecholamines)
RN  - 0 (Neurotoxins)
RN  - 333DO1RDJY (Serotonin)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/analogs & derivatives/*pharmacology
MH  - Amphetamines/*pharmacology
MH  - Animals
MH  - Axons/*drug effects/ultrastructure
MH  - Catecholamines/metabolism
MH  - Cell Survival
MH  - Diencephalon/metabolism/*ultrastructure
MH  - Immunohistochemistry
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine
MH  - Nerve Degeneration
MH  - Neurotoxins/pharmacology
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Serotonin/metabolism/*physiology
MH  - Staining and Labeling
MH  - Telencephalon/metabolism/*ultrastructure
PMC - PMC6569396
EDAT- 1988/08/01 00:00
MHDA- 1988/08/01 00:01
PMCR- 1989/02/01
CRDT- 1988/08/01 00:00
PHST- 1988/08/01 00:00 [pubmed]
PHST- 1988/08/01 00:01 [medline]
PHST- 1988/08/01 00:00 [entrez]
PHST- 1989/02/01 00:00 [pmc-release]
AID - 10.1523/JNEUROSCI.08-08-02788.1988 [doi]
PST - ppublish
SO  - J Neurosci. 1988 Aug;8(8):2788-803. doi: 10.1523/JNEUROSCI.08-08-02788.1988.