PMID- 2893986
OWN - NLM
STAT- MEDLINE
DCOM- 19880407
LR  - 20190726
IS  - 0028-3908 (Print)
IS  - 0028-3908 (Linking)
VI  - 26
IP  - 12
DP  - 1987 Dec
TI  - Immediate and long-term effects of 3,4-methylenedioxymethamphetamine on serotonin 
      pathways in brain of rat.
PG  - 1677-83
AB  - In the rat, administration of the psychoactive analog of amphetamine 
      3,4-methylenedioxymethamphetamine (MDMA), causes selective, pronounced decreases 
      in markers of central serotonergic function. The time course of these 
      neurochemical changes was examined in several serotonergic nerve terminal regions 
      of the brain. Fifteen min after subcutaneous injection of MDMA (10 mg/kg), the 
      enzymatic activity of tryptophan hydroxylase (the rate-limiting enzyme for the 
      biosynthesis of serotonin) was significantly decreased in the frontal cortex; by 
      1 hr after the injection, the activity of tryptophan hydroxylase had 
      significantly declined in the neostriatum, hippocampus and hypothalamus as well. 
      Although extensive recovery had occurred by 2 weeks, the activity of the enzyme 
      remained significantly depressed in most regions. Decline of the regional content 
      of 5-hydroxytryptamine (5-HT) closely paralleled, but was usually preceded by, 
      that of the enzyme. Concentrations of the primary metabolite of 5-HT, 
      5-hydroxyindoleacetic acid (5-HIAA), were less responsive: in most regions levels 
      of 5-HIAA had significantly decreased by 3 hr, but not by 1 hr, following 
      treatment. Markers of dopamine function were altered transiently but had returned 
      to control values by 24 hr. Administration of multiple doses of MDMA (5 doses 
      over a 24-hr period) resulted in significant decreases in serotonergic parameters 
      for up to 110 days after treatment. The rate and extent of recovery varied 
      according to both the dose administered and the region examined. The persistence 
      of these serotonergic deficits suggests that MDMA induced the destruction of 
      serotonin-containing axon terminals.
FAU - Stone, D M
AU  - Stone DM
AD  - Department of Pharmacology and Toxicology, University of Utah.
FAU - Merchant, K M
AU  - Merchant KM
FAU - Hanson, G R
AU  - Hanson GR
FAU - Gibb, J W
AU  - Gibb JW
LA  - eng
GR  - DA 04222/DA/NIDA NIH HHS/United States
GR  - DA 08869/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Amphetamines)
RN  - 0 (Biogenic Amines)
RN  - 333DO1RDJY (Serotonin)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - EC 1.14.16.4 (Tryptophan Hydroxylase)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/analogs & derivatives/*pharmacology
MH  - Amphetamines/*pharmacology
MH  - Animals
MH  - Biogenic Amines/metabolism
MH  - Brain/drug effects/metabolism/*physiology
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine
MH  - Neural Pathways/*drug effects
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Serotonin/*physiology
MH  - Time Factors
MH  - Tryptophan Hydroxylase/metabolism
EDAT- 1987/12/01 00:00
MHDA- 1987/12/01 00:01
CRDT- 1987/12/01 00:00
PHST- 1987/12/01 00:00 [pubmed]
PHST- 1987/12/01 00:01 [medline]
PHST- 1987/12/01 00:00 [entrez]
AID - 10.1016/0028-3908(87)90117-1 [doi]
PST - ppublish
SO  - Neuropharmacology. 1987 Dec;26(12):1677-83. doi: 10.1016/0028-3908(87)90117-1.