PMID- 17602794
OWN - NLM
STAT- MEDLINE
DCOM- 20071221
LR  - 20151119
IS  - 0197-0186 (Print)
IS  - 0197-0186 (Linking)
VI  - 51
IP  - 8
DP  - 2007 Dec
TI  - Short-term effects of 3,4-methylen-dioxy-metamphetamine (MDMA) on 5-HT(1A) 
      receptors in the rat hippocampus.
PG  - 496-506
AB  - The first effects of 3,4-methylen-dioxy-metamphetamine (MDMA, "ecstasy"), on 
      serotonin 1A (5-HT(1A)) receptors in rat hippocampus were determined by means of 
      [(3)H]-8-hydroxy-dipropylamino-tetralin ([(3)H]-8-OH-DPAT) and 
      5'guanosine-(gamma-[(35)S]-thio)triphosphate ([(35)S]-GTPgammaS) binding as well 
      as inhibition of forskolin (FK)-stimulated adenylyl cyclase (AC) activity. The 
      study was completed by [(35)S]-GTPgammaS functional autoradiography experiments 
      carried out in frontal sections of rat brain, including the hippocampal region. 
      Results showed that MDMA was either able to displace [(3)H]-8-OH-DPAT binding 
      (K(i) congruent with 500 nM) or to reduce the number of specific sites (B(max)) 
      without affecting K(d). The drug also failed to change the [(35)S]-GTPgammaS 
      binding or to inhibit AC velocity, underlying its behavior as a non-competitive 
      5-HT(1A) receptor antagonist. Further, MDMA (1 or 100 microM), partially 
      antagonized either [(35)S]-GTPgammaS binding stimulation of the agonists 5CT and 
      8-OH-DPAT or the AC inhibition induced by 5CT and DP-5CT. However, in contrast to 
      binding studies, in AC assays the amphetamine displayed an effect also on EC(50), 
      always being less potent than the reference antagonist WAY100,635. In functional 
      autoradiography, MDMA behaved either as a partial 5-HT(1A) antagonist in limbic 
      areas or, added alone, as an agonist, increasing the coupling signal presumably 
      through 5-HT release from synapses. Interestingly, the selective 5-HT re-uptake 
      inhibitor (SSRI) fluoxetine had no effect on MDMA [(35)S]-GTPgammaS binding 
      activation. This latter finding indicates that the amphetamine can release 5-HT 
      via alternative mechanisms to 5-HT transporter binding, probably via membrane 
      synaptic receptors or vesicular transporters. The release of other transmitters 
      is not excluded. Therefore, our results encourage at extending the study of MDMA 
      biochemical profiles, in the attempt to elucidate those amphetamine-induced 
      pathways with a potential for neurotoxicity or psycho-stimulant activity.
FAU - Giannaccini, Gino
AU  - Giannaccini G
AD  - Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, 
      University of Pisa, Via Bonanno 6, Pisa 56126, Italy. ggino@farm.unipi.it
FAU - Betti, Laura
AU  - Betti L
FAU - Pirone, Andrea
AU  - Pirone A
FAU - Palego, Lionella
AU  - Palego L
FAU - Fabiani, Ortenzio
AU  - Fabiani O
FAU - Fabbrini, Laura
AU  - Fabbrini L
FAU - Mascia, Giovanni
AU  - Mascia G
FAU - Giusti, Laura
AU  - Giusti L
FAU - Macchia, Marco
AU  - Macchia M
FAU - Giusiani, Mario
AU  - Giusiani M
FAU - Martini, Claudia
AU  - Martini C
FAU - Lucacchini, Antonio
AU  - Lucacchini A
LA  - eng
PT  - Journal Article
DEP - 20070531
PL  - England
TA  - Neurochem Int
JT  - Neurochemistry international
JID - 8006959
RN  - 0 (Adenylyl Cyclase Inhibitors)
RN  - 0 (Dopamine Agents)
RN  - 0 (Serotonin Agents)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 112692-38-3 (Receptor, Serotonin, 5-HT1A)
RN  - 333DO1RDJY (Serotonin)
RN  - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate))
RN  - 78950-78-4 (8-Hydroxy-2-(di-n-propylamino)tetralin)
RN  - CK833KGX7E (Amphetamine)
RN  - EC 4.6.1.1 (Adenylyl Cyclases)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - 8-Hydroxy-2-(di-n-propylamino)tetralin/metabolism
MH  - Adenylyl Cyclase Inhibitors
MH  - Adenylyl Cyclases/metabolism
MH  - Amphetamine/pharmacology
MH  - Animals
MH  - Binding Sites/drug effects/physiology
MH  - Binding, Competitive/*drug effects/physiology
MH  - Brain Chemistry/drug effects/physiology
MH  - Dopamine Agents/pharmacology
MH  - Guanosine 5'-O-(3-Thiotriphosphate)/metabolism
MH  - Hippocampus/*drug effects/metabolism
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Radioligand Assay
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Serotonin, 5-HT1A/*drug effects/metabolism
MH  - Serotonin/metabolism
MH  - Serotonin Agents/*pharmacology
MH  - Serotonin Plasma Membrane Transport Proteins/drug effects/metabolism
MH  - Synaptic Transmission/drug effects/physiology
MH  - Time Factors
EDAT- 2007/07/03 09:00
MHDA- 2007/12/22 09:00
CRDT- 2007/07/03 09:00
PHST- 2007/04/23 00:00 [received]
PHST- 2007/05/11 00:00 [accepted]
PHST- 2007/07/03 09:00 [pubmed]
PHST- 2007/12/22 09:00 [medline]
PHST- 2007/07/03 09:00 [entrez]
AID - S0197-0186(07)00127-1 [pii]
AID - 10.1016/j.neuint.2007.05.010 [doi]
PST - ppublish
SO  - Neurochem Int. 2007 Dec;51(8):496-506. doi: 10.1016/j.neuint.2007.05.010. Epub 
      2007 May 31.