PMID- 14511335
OWN - NLM
STAT- MEDLINE
DCOM- 20031205
LR  - 20190815
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 18
IP  - 6
DP  - 2003 Sep
TI  - Endogenous 5-HT, released by MDMA through serotonin transporter- and secretory 
      vesicle-dependent mechanisms, reduces hippocampal excitatory synaptic 
      transmission by preferential activation of 5-HT1B receptors located on CA1 
      pyramidal neurons.
PG  - 1559-71
AB  - A multitude of different serotonin (5-HT) receptor types are expressed in the 
      hippocampus, but the identity of receptors actually mediating the physiological 
      response to endogenous 5-HT has not been determined. We combined 
      pharmacologically induced release of 5-HT with patch-clamp recordings on 
      disinhibited rat CA1 minislices to determine effects of endogenous 5-HT on the 
      excitability of pyramidal neurons and synaptic transmission among them. We found 
      that application of 5-HT releasers, 3,4-methylenedioxy-methamphetamine (MDMA) or 
      p-methylthioamphetamine, at concentrations ranging from 2 to 50 microm, reduced 
      the excitatory synaptic transmission between CA1 pyramidal neurons without 
      altering their basal electrical properties. This effect of MDMA was blocked by 
      the selective 5-HT1B antagonist GR 55562, was dependent on endogenous 5-HT 
      content and was mediated by presynaptically located, pertussis-toxin sensitive 
      mechanisms. We found no other MDMA effects in our preparation, which indicates 
      that the release of endogenous 5-HT preferentially stimulates 5-HT1B receptors on 
      CA1 pyramidal neurons. Therefore, 5-HT1B receptor activation may represent a 
      predominant component of the physiological response to endogenous 5-HT in the 
      CA1. The high sensitivity of the 5-HT1B receptor-mediated reduction of 
      polysynaptic excitatory responses to the extracellular 5-HT level enabled us to 
      study mechanisms of the 5-HT releasing action of MDMA. Block of the serotonin 
      transporter (SERT) with citalopram slowed the time course and reduced overall 
      5-HT release by MDMA. Depletion of vesicular 5-HT, by inhibition of vesicular 
      monoamine transporter type 2 with tetrabenazine prevented the release. Thus 
      although the SERT reversal contributes, a direct vesicle-depleting action is 
      essential for MDMA release of 5-HT.
FAU - Mlinar, Boris
AU  - Mlinar B
AD  - Department of Preclinical and Clinical Pharmacology Mario Aiazzi-Mancini 
      University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy. 
      bmlinar@unifi.it
FAU - Corradetti, Renato
AU  - Corradetti R
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Carrier Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (GABA Antagonists)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Receptor, Serotonin, 5-HT1B)
RN  - 0 (Serotonin Agents)
RN  - 0 (Serotonin Antagonists)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Slc6a4 protein, rat)
RN  - 333DO1RDJY (Serotonin)
RN  - EC 2.4.2.31 (Pertussis Toxin)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Carrier Proteins/*physiology
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Electric Stimulation
MH  - Enzyme Inhibitors/pharmacology
MH  - Excitatory Postsynaptic Potentials/drug effects
MH  - GABA Antagonists/pharmacology
MH  - Hippocampus/cytology/physiology
MH  - In Vitro Techniques
MH  - Membrane Glycoproteins/*physiology
MH  - Membrane Potentials/drug effects
MH  - *Membrane Transport Proteins
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - *Nerve Tissue Proteins
MH  - Neural Conduction/drug effects
MH  - Pertussis Toxin/pharmacology
MH  - Pyramidal Cells/*drug effects/metabolism/physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Serotonin, 5-HT1B/*metabolism
MH  - Secretory Vesicles/*drug effects/metabolism
MH  - Serotonin/*metabolism
MH  - Serotonin Agents/*pharmacology
MH  - Serotonin Antagonists/pharmacology
MH  - Serotonin Plasma Membrane Transport Proteins
MH  - Synaptic Transmission/*drug effects/physiology
MH  - Time Factors
EDAT- 2003/09/27 05:00
MHDA- 2003/12/06 05:00
CRDT- 2003/09/27 05:00
PHST- 2003/09/27 05:00 [pubmed]
PHST- 2003/12/06 05:00 [medline]
PHST- 2003/09/27 05:00 [entrez]
AID - 2884 [pii]
AID - 10.1046/j.1460-9568.2003.02884.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2003 Sep;18(6):1559-71. doi: 10.1046/j.1460-9568.2003.02884.x.