PMID- 22766162
OWN - NLM
STAT- MEDLINE
DCOM- 20130129
LR  - 20161125
IS  - 1095-9572 (Electronic)
IS  - 1053-8119 (Linking)
VI  - 63
IP  - 1
DP  - 2012 Oct 15
TI  - Imaging DA release in a rat model of L-DOPA-induced dyskinesias: a longitudinal 
      in vivo PET investigation of the antidyskinetic effect of MDMA.
PG  - 423-33
LID - 10.1016/j.neuroimage.2012.06.051 [doi]
AB  - In the context of Parkinson's disease, motor symptoms result from the 
      degeneration of nigrostriatal neurons. Dopamine (DA) replacement using 
      l-3,4-dihydroxyphenylalanine (L-DOPA) has been the treatment of choice in the 
      early stages of the disease. However, with disease progression, patients suffer 
      from motor complications, which have been suggested to arise from DA released 
      from serotonergic terminals according to the false neurotransmitter hypothesis. 
      The synthetic amphetamine derivative (+/-) 3,4-methylenedioxymethamphetamine (MDMA) 
      has been shown to significantly inhibit dyskinesia in humans and in animal models 
      of PD. In this study, we examined the effect of MDMA on L-DOPA-induced DA release 
      by using [(11)C]raclopride kinetic modeling to assess alterations in DA 
      neurotransmission in a rat model of L-DOPA-induced dyskinesia (LID) in a 
      longitudinal in vivo PET study. Rats were submitted to 6-OHDA lesions, and the 
      lesions were confirmed to be sufficiently severe based on the performance during 
      stepping tests and [(11)C]methylphenidate PET scans. The rats underwent two 
      [(11)C]raclopride PET sessions before (baseline) and after two weeks of chronic 
      L-DOPA treatment (priming). L-DOPA priming led to strong abnormal involuntary 
      movements (AIMs). In group 1, L-DOPA priming reduced L-DOPA-induced DA release in 
      the lesioned striatum with no effect on the healthy side, while the concomitant 
      administration of L-DOPA and MDMA (group 2) increased the DA levels in the 
      lesioned and healthy striatum. In addition, behavioral analysis, which was 
      performed two weeks after the second PET session, confirmed the antidyskinetic 
      effect of MDMA. Our data show that L-DOPA-induced DA release is attenuated in the 
      Parkinsonian striatum after chronic L-DOPA pretreatment and that the 
      antidyskinetic mechanism of MDMA does not depend primarily on dopaminergic 
      neurotransmission.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Lettfuss, Nadine Y
AU  - Lettfuss NY
AD  - Neuropharmacology, Eberhard Karls University Tuebingen, Germany. 
      nadine.lettfuss@uni-tuebingen.de
FAU - Fischer, Kristina
AU  - Fischer K
FAU - Sossi, Vesna
AU  - Sossi V
FAU - Pichler, Bernd J
AU  - Pichler BJ
FAU - von Ameln-Mayerhofer, Andreas
AU  - von Ameln-Mayerhofer A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120702
PL  - United States
TA  - Neuroimage
JT  - NeuroImage
JID - 9215515
RN  - 0 (Adrenergic Uptake Inhibitors)
RN  - 46627O600J (Levodopa)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Adrenergic Uptake Inhibitors/therapeutic use
MH  - Animals
MH  - Brain/diagnostic imaging/drug effects/*metabolism
MH  - Dopamine/*metabolism
MH  - Dyskinesia, Drug-Induced/diagnostic imaging/*metabolism/*prevention & control
MH  - *Levodopa
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*therapeutic use
MH  - Positron-Emission Tomography/*methods
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2012/07/07 06:00
MHDA- 2013/01/30 06:00
CRDT- 2012/07/07 06:00
PHST- 2012/02/06 00:00 [received]
PHST- 2012/06/03 00:00 [revised]
PHST- 2012/06/26 00:00 [accepted]
PHST- 2012/07/07 06:00 [entrez]
PHST- 2012/07/07 06:00 [pubmed]
PHST- 2013/01/30 06:00 [medline]
AID - S1053-8119(12)00667-2 [pii]
AID - 10.1016/j.neuroimage.2012.06.051 [doi]
PST - ppublish
SO  - Neuroimage. 2012 Oct 15;63(1):423-33. doi: 10.1016/j.neuroimage.2012.06.051. Epub 
      2012 Jul 2.