PMID- 2452449
OWN - NLM
STAT- MEDLINE
DCOM- 19880609
LR  - 20220310
IS  - 0091-3057 (Print)
IS  - 0091-3057 (Linking)
VI  - 29
IP  - 2
DP  - 1988 Feb
TI  - MDMA-induced neurotoxicity: parameters of degeneration and recovery of brain 
      serotonin neurons.
PG  - 269-74
AB  - This study investigates a number of parameters that influence the neurotoxic 
      effects of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin (5-HT) neurons 
      in brain. Both the dose and number of injections of MDMA affect the degree of 
      neurotoxicity on 5-HT axons and terminals as assessed by decreases in the content 
      of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) and the density of 5-HT uptake 
      sites. Repeated systemic administration of various doses of MDMA (5-20 mg/kg 
      twice daily for 4 consecutive days) results in dose-dependent decreases in 5-HT, 
      5-HIAA and 5-HT uptake sites. Increasing the number of injections of MDMA 
      resulted in progressively greater reductions in 5-HT and 5-HIAA which occurred 
      prior to decreases in 5-HT uptake sites. In contrast, no significant changes were 
      observed in the density of norepinephrine uptake sites following single or 
      repeated injections of 20 mg/kg MDMA. With respect to neuronal regeneration, 
      following an initial 90% loss of 5-HT uptake sites after treatment with MDMA, the 
      recovery of these sites occurred over a protracted period of time; a marked 25% 
      reduction was seen at 6 months and the concentration of 5-HT uptake sites 
      returned to control levels at 12 months following treatment with MDMA. 
      Pretreatment with the selective 5-HT uptake blocker, citalopram, prior to each 
      injection of MDMA prevented the neurotoxic effects of MDMA on the 5-HT parameters 
      described above suggesting that active uptake of MDMA or a MDMA-related substance 
      into brain 5-HT neurons was involved in the neurotoxic actions of the drug. In 
      addition, the neurodegenerative effects of MDMA on 5-HT neurons exhibited some 
      species specificity as comparable decreases in cerebral cortical 5-HT, 5-HIAA and 
      5-HT uptake sites were observed in rat and guinea pig while no significant 
      changes in any of these serotonergic parameters were seen in mouse brain.
FAU - Battaglia, G
AU  - Battaglia G
AD  - Neuroscience Branch, National Institute on Drug Abuse, Baltimore, MD 21224.
FAU - Yeh, S Y
AU  - Yeh SY
FAU - De Souza, E B
AU  - De Souza EB
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Pharmacol Biochem Behav
JT  - Pharmacology, biochemistry, and behavior
JID - 0367050
RN  - 0 (Amphetamines)
RN  - 333DO1RDJY (Serotonin)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - 54-16-0 (Hydroxyindoleacetic Acid)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/administration & dosage/analogs & 
      derivatives/*toxicity
MH  - Amphetamines/*toxicity
MH  - Animals
MH  - Biological Transport, Active/drug effects
MH  - Brain/*drug effects/physiology
MH  - Dose-Response Relationship, Drug
MH  - Guinea Pigs
MH  - Hydroxyindoleacetic Acid/metabolism
MH  - Male
MH  - Mice
MH  - N-Methyl-3,4-methylenedioxyamphetamine
MH  - Nerve Degeneration/drug effects
MH  - Nerve Regeneration/drug effects
MH  - Neurons/drug effects/physiology
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Serotonin/*metabolism
MH  - Species Specificity
EDAT- 1988/02/01 00:00
MHDA- 1988/02/01 00:01
CRDT- 1988/02/01 00:00
PHST- 1988/02/01 00:00 [pubmed]
PHST- 1988/02/01 00:01 [medline]
PHST- 1988/02/01 00:00 [entrez]
AID - 0091-3057(88)90155-4 [pii]
AID - 10.1016/0091-3057(88)90155-4 [doi]
PST - ppublish
SO  - Pharmacol Biochem Behav. 1988 Feb;29(2):269-74. doi: 
      10.1016/0091-3057(88)90155-4.