PMID- 18611291
OWN - NLM
STAT- MEDLINE
DCOM- 20090126
LR  - 20221207
IS  - 1461-1457 (Print)
IS  - 1461-1457 (Linking)
VI  - 11
IP  - 8
DP  - 2008 Dec
TI  - Differential long-term effects of MDMA on the serotoninergic system and 
      hippocampal cell proliferation in 5-HTT knock-out vs. wild-type mice.
PG  - 1149-62
LID - 10.1017/S1461145708009048 [doi]
AB  - Although numerous studies investigated the mechanisms underlying 
      3,4-methylenedioxymethamphetamine (MDMA)-induced neurotoxicity, little is known 
      about its long-term functional consequences on 5-HT neurotransmission in mice. 
      This led us to evaluate the delayed effects of MDMA exposure on the 5-HT system, 
      using in-vitro and in-vivo approaches in both 5-HTT wild-type and knock-out mice. 
      Acute MDMA in-vitro application on slices of the dorsal raphe nucleus (DRN) 
      induced concentration-dependent 5-HT release and 5-HT cell firing inhibition. 
      Four weeks after MDMA administration (20 mg/kg b.i.d for 4 d), a 2-fold increase 
      in the potency of the 5-HT1A receptor agonist ipsapirone to inhibit the discharge 
      of DRN 5-HT neurons and a larger hypothermic response to 8-OH-DPAT were observed 
      in MDMA- compared to saline-treated mice. This adaptive 5-HT1A autoreceptor 
      supersensitivity was associated with decreases in 5-HT levels but no changes of 
      [3H]citalopram binding in brain. Long-term MDMA treatment also induced a 30% 
      decrease in BrdU labelling of proliferating hippocampal cells and an increased 
      immobility duration in the forced swim test suggesting a depressive-like 
      behaviour induced by MDMA treatment. All these effects were abolished in 5-HTT-/- 
      knock-out mice. These data indicated that, in mice, MDMA administration induced a 
      delayed adaptive supersensitivity of 5-HT1A autoreceptors in the DRN, a deficit 
      in hippocampal cell proliferation and a depressive-like behaviour. These 
      5-HTT-dependent effects, opposite to those of antidepressants, might contribute 
      to MDMA-induced mood disorders.
FAU - Renoir, Thibault
AU  - Renoir T
AD  - INSERM, U677, Paris, F-75013, France.
FAU - Paizanis, Eleni
AU  - Paizanis E
FAU - El Yacoubi, Malika
AU  - El Yacoubi M
FAU - Saurini, Francoise
AU  - Saurini F
FAU - Hanoun, Naima
AU  - Hanoun N
FAU - Melfort, Maxette
AU  - Melfort M
FAU - Lesch, Klaus Peter
AU  - Lesch KP
FAU - Hamon, Michel
AU  - Hamon M
FAU - Lanfumey, Laurence
AU  - Lanfumey L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080709
PL  - England
TA  - Int J Neuropsychopharmacol
JT  - The international journal of neuropsychopharmacology
JID - 9815893
RN  - 0 (Hallucinogens)
RN  - 0 (Receptor, Serotonin, 5-HT2A)
RN  - 0 (Serotonin Agents)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 0 (Slc6a4 protein, mouse)
RN  - 0DHU5B8D6V (Citalopram)
RN  - 333DO1RDJY (Serotonin)
RN  - 78950-78-4 (8-Hydroxy-2-(di-n-propylamino)tetralin)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - 8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology
MH  - Animals
MH  - Cell Proliferation/drug effects
MH  - Citalopram/metabolism
MH  - Electrophysiology
MH  - Female
MH  - Hallucinogens/*pharmacology
MH  - Hindlimb Suspension/psychology
MH  - Hippocampus/*cytology/drug effects/metabolism
MH  - Injections, Intraperitoneal
MH  - Male
MH  - Membranes/drug effects/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Patch-Clamp Techniques
MH  - Raphe Nuclei/cytology/drug effects
MH  - Receptor, Serotonin, 5-HT2A/drug effects/genetics/physiology
MH  - Serotonin/metabolism/*physiology
MH  - Serotonin Agents/*pharmacology
MH  - Serotonin Plasma Membrane Transport Proteins/*genetics/*physiology
MH  - Serotonin Receptor Agonists/pharmacology
MH  - Selective Serotonin Reuptake Inhibitors/metabolism
MH  - Swimming/psychology
EDAT- 2008/07/10 09:00
MHDA- 2009/01/27 09:00
CRDT- 2008/07/10 09:00
PHST- 2008/07/10 09:00 [pubmed]
PHST- 2009/01/27 09:00 [medline]
PHST- 2008/07/10 09:00 [entrez]
AID - S1461145708009048 [pii]
AID - 10.1017/S1461145708009048 [doi]
PST - ppublish
SO  - Int J Neuropsychopharmacol. 2008 Dec;11(8):1149-62. doi: 
      10.1017/S1461145708009048. Epub 2008 Jul 9.