PMID- 17306775
OWN - NLM
STAT- MEDLINE
DCOM- 20080102
LR  - 20191210
IS  - 0006-3223 (Print)
IS  - 0006-3223 (Linking)
VI  - 62
IP  - 6
DP  - 2007 Sep 15
TI  - 3,4-methylenedioxymethamphetamine self-administration is abolished in serotonin 
      transporter knockout mice.
PG  - 669-79
AB  - BACKGROUND: The neurobiological mechanism underlying the reinforcing effects of 
      3,4-methylenedioxymethamphetamine (MDMA) remains unclear. The aim of the present 
      study was to determine the contribution of the serotonin transporter (SERT) in 
      MDMA self-administration behavior by using knockout (KO) mice deficient in SERT. 
      METHODS: Knockout mice and wild-type (WT) littermates were trained to acquire 
      intravenous self-administration of MDMA (0, .03, .06, .125, and .25 
      mg/kg/infusion) on a fixed ratio 1 (FR1) schedule of reinforcement. Additional 
      groups of mice were trained to obtain food and water to rule out operant 
      responding impairments. Microdialysis studies were performed to evaluate dopamine 
      (DA) and serotonin (5-HT) extracellular levels in the nucleus accumbens (NAC) and 
      prefrontal cortex (PFC), respectively, after acute MDMA (10 mg/kg). RESULTS: None 
      of the MDMA doses tested maintained intravenous self-administration in KO 
      animals, whereas WT mice acquired responding for MDMA. Acquisition of operant 
      responding for food and water was delayed in KO mice, but no differences between 
      genotypes were observed on the last day of training. MDMA increased DA 
      extracellular levels to a similar extent in the NAC of WT and KO mice. 
      Conversely, extracellular concentrations of 5-HT in the PFC were increased 
      following MDMA only in WT mice. CONCLUSIONS: These findings provide evidence for 
      the specific involvement of SERT in MDMA reinforcing properties.
FAU - Trigo, Jose Manuel
AU  - Trigo JM
AD  - Laboratori de Neurofarmacologia, Departament de Ciencies Experimentals i de la 
      Salut, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
FAU - Renoir, Thibault
AU  - Renoir T
FAU - Lanfumey, Laurence
AU  - Lanfumey L
FAU - Hamon, Michel
AU  - Hamon M
FAU - Lesch, Klaus-Peter
AU  - Lesch KP
FAU - Robledo, Patricia
AU  - Robledo P
FAU - Maldonado, Rafael
AU  - Maldonado R
LA  - eng
GR  - 5R01 DA 016768/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070216
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 0 (Hallucinogens)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 333DO1RDJY (Serotonin)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/drug effects/physiology
MH  - Conditioning, Operant/physiology
MH  - Dopamine/metabolism
MH  - Extracellular Space/metabolism
MH  - Hallucinogens/*administration & dosage/pharmacology
MH  - Injections, Intravenous
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Microdialysis
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*administration & dosage/pharmacology
MH  - Nucleus Accumbens/metabolism
MH  - Prefrontal Cortex/metabolism
MH  - *Reinforcement, Psychology
MH  - Reward
MH  - *Self Administration
MH  - Serotonin/metabolism
MH  - Serotonin Plasma Membrane Transport Proteins/*physiology
EDAT- 2007/02/20 09:00
MHDA- 2008/01/03 09:00
CRDT- 2007/02/20 09:00
PHST- 2006/07/17 00:00 [received]
PHST- 2006/11/06 00:00 [revised]
PHST- 2006/11/08 00:00 [accepted]
PHST- 2007/02/20 09:00 [pubmed]
PHST- 2008/01/03 09:00 [medline]
PHST- 2007/02/20 09:00 [entrez]
AID - S0006-3223(06)01445-4 [pii]
AID - 10.1016/j.biopsych.2006.11.005 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2007 Sep 15;62(6):669-79. doi: 10.1016/j.biopsych.2006.11.005. 
      Epub 2007 Feb 16.