PMID- 20942998
OWN - NLM
STAT- MEDLINE
DCOM- 20111110
LR  - 20191210
IS  - 1469-5111 (Electronic)
IS  - 1461-1457 (Linking)
VI  - 14
IP  - 7
DP  - 2011 Aug
TI  - Involvement of 5-HT2A receptors in MDMA reinforcement and cue-induced 
      reinstatement of MDMA-seeking behaviour.
PG  - 927-40
LID - 10.1017/S1461145710001215 [doi]
AB  - The serotonergic system appears crucial for (+/-)-3,4-methylenedioxymethamphetamine 
      (MDMA) reinforcing properties. Current evidence indicates that serotonin 5-HT2A 
      receptors (5-HT2ARs) modulate mesolimbic dopamine (DA) activity and several 
      behavioural responses related to the addictive properties of psychostimulants. 
      This study evaluated the role of 5-HT2ARs in MDMA-induced reinforcement and 
      hyperlocomotion, and the reinstatement of MDMA-seeking behaviour. Basal and 
      MDMA-stimulated extracellular levels of DA in the nucleus accumbens (NAc) and 
      serotonin and noradrenaline in the prefrontal cortex were also assessed. 
      Self-administration of MDMA was blunted in 5-HT2AR knockout (KO) mice compared to 
      wild-type (WT) littermates at both doses tested (0.125 and 0.25 mg/kg per 
      infusion). Horizontal locomotion was increased by MDMA (10 and 20 mg/kg i.p.) to 
      a higher extent in KO than in WT mice. DA outflow in the NAc was lower in KO 
      compared to WT mice under basal conditions and after MDMA (20 mg/kg) challenge. 
      In WT mice, MDMA (5 and 10 mg/kg i.p.) priming did not reinstate MDMA-seeking 
      behaviour, while cue-induced reinstatement was prominent. This cue-induced 
      reinstatement was blocked by administration of the selective 5-HT2AR antagonist, 
      SR46349B (eplivanserin) at a dose of 0.5 mg/kg, but not at 0.25 mg/kg. Our 
      results indicate that 5-HT2ARs are crucial for MDMA-induced reinforcement and 
      cue-induced reinstatement of MDMA-seeking behaviour. These effects are probably 
      due to the modulation of mesolimbic dopaminergic activity.
FAU - Orejarena, Maria Juliana
AU  - Orejarena MJ
AD  - Universitat Pompeu Fabra, Barcelona, Spain.
FAU - Lanfumey, Laurence
AU  - Lanfumey L
FAU - Maldonado, Rafael
AU  - Maldonado R
FAU - Robledo, Patricia
AU  - Robledo P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101014
PL  - England
TA  - Int J Neuropsychopharmacol
JT  - The international journal of neuropsychopharmacology
JID - 9815893
RN  - 0 (Fluorobenzenes)
RN  - 0 (Phenols)
RN  - 0 (Receptor, Serotonin, 5-HT2A)
RN  - 0 (Serotonin 5-HT2 Receptor Agonists)
RN  - 0 (Serotonin 5-HT2 Receptor Antagonists)
RN  - 130580-02-8 (SR 46349B)
RN  - 333DO1RDJY (Serotonin)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Animals
MH  - Behavior, Addictive/*chemically induced/genetics/physiopathology
MH  - Cues
MH  - Dopamine/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Extinction, Psychological/*drug effects
MH  - Female
MH  - Fluorobenzenes/pharmacology
MH  - Locomotion/drug effects/physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage/*pharmacology
MH  - Norepinephrine/metabolism
MH  - Nucleus Accumbens/drug effects/metabolism
MH  - Phenols/pharmacology
MH  - Prefrontal Cortex/drug effects/metabolism
MH  - Receptor, Serotonin, 5-HT2A/genetics/*physiology
MH  - *Reinforcement, Psychology
MH  - Self Administration
MH  - Serotonin/metabolism
MH  - Serotonin 5-HT2 Receptor Agonists/administration & dosage/pharmacology
MH  - Serotonin 5-HT2 Receptor Antagonists/pharmacology
EDAT- 2010/10/15 06:00
MHDA- 2011/11/11 06:00
CRDT- 2010/10/15 06:00
PHST- 2010/10/15 06:00 [entrez]
PHST- 2010/10/15 06:00 [pubmed]
PHST- 2011/11/11 06:00 [medline]
AID - S1461145710001215 [pii]
AID - 10.1017/S1461145710001215 [doi]
PST - ppublish
SO  - Int J Neuropsychopharmacol. 2011 Aug;14(7):927-40. doi: 
      10.1017/S1461145710001215. Epub 2010 Oct 14.