PMID- 9517441
OWN - NLM
STAT- MEDLINE
DCOM- 19980505
LR  - 20190726
IS  - 0028-3908 (Print)
IS  - 0028-3908 (Linking)
VI  - 36
IP  - 11-12
DP  - 1997 Nov-Dec
TI  - Acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on 5-HT cell firing and 
      release: comparison between dorsal and median raphe 5-HT systems.
PG  - 1697-703
AB  - It is proposed that 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) is more 
      toxic to 5-HT neurones projecting from the dorsal raphe nucleus (DRN) than to 
      those from the median raphe nucleus (MRN). Since increased 5-HT release has been 
      associated with MDMA-induced neurotoxicity, MDMA may have a DRN-selective 5-HT 
      releasing effect. Here we have compared the effects of acute MDMA on DRN and MRN 
      5-HT pathways using in vivo electrophysiological and neurochemical techniques. 
      MDMA inhibited the firing of 5-HT neurones in both the DRN and the MRN, and did 
      so with similar potency (ED50 values, 0.589 +/- 0.151 (8) and 0.588 +/- 0.207 (6) 
      mg/kg i.v., respectively). In both nuclei this inhibitory effect was reversed by 
      the selective 5-HT1A receptor antagonist, WAY 100635 (0.1 mg/kg i.v.). 
      Microdialysis measurements were made in the frontal cortex and dorsal 
      hippocampus, regions which receive a DRN- and an MRN-selective 5-HT innervation, 
      respectively. A dose of 1 mg/kg i.v. MDMA increased extracellular 5-HT 3-fold in 
      both the frontal cortex and dorsal hippocampus. A higher dose (3 mg/kg i.v.) 
      increased 5-HT levels 8-fold in both regions. Overall, our data suggest that MDMA 
      releases 5-HT from the cell body and terminal regions of both DRN and MRN 5-HT 
      pathways, and does so in a qualitatively and quantitatively similar fashion. We 
      conclude that any DRN-selectivity in the neurotoxic effects of MDMA is not due to 
      a DRN-selective, acute 5-HT releasing action of the drug.
FAU - Gartside, S E
AU  - Gartside SE
AD  - University of Oxford Department of Clinical Pharmacology, Radcliffe Infirmary, 
      UK.
FAU - McQuade, R
AU  - McQuade R
FAU - Sharp, T
AU  - Sharp T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Piperazines)
RN  - 0 (Pyridines)
RN  - 0 (Serotonin Agents)
RN  - 0 (Serotonin Antagonists)
RN  - 333DO1RDJY (Serotonin)
RN  - 71IH826FEG 
      (N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Chromatography, High Pressure Liquid
MH  - Electric Stimulation
MH  - Electrochemistry
MH  - Electrophysiology
MH  - Hippocampus/drug effects/metabolism
MH  - Microdialysis
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Neurons/*drug effects/metabolism
MH  - Piperazines/pharmacology
MH  - Prefrontal Cortex/drug effects/metabolism
MH  - Pyridines/pharmacology
MH  - Raphe Nuclei/cytology/drug effects/*physiology
MH  - Serotonin/metabolism/*physiology
MH  - Serotonin Agents/*pharmacology
MH  - Serotonin Antagonists/pharmacology
MH  - Stereotaxic Techniques
EDAT- 1998/03/28 00:00
MHDA- 1998/03/28 00:01
CRDT- 1998/03/28 00:00
PHST- 1998/03/28 00:00 [pubmed]
PHST- 1998/03/28 00:01 [medline]
PHST- 1998/03/28 00:00 [entrez]
AID - 10.1016/s0028-3908(97)00171-8 [doi]
PST - ppublish
SO  - Neuropharmacology. 1997 Nov-Dec;36(11-12):1697-703. doi: 
      10.1016/s0028-3908(97)00171-8.