PMID- 22260267
OWN - NLM
STAT- MEDLINE
DCOM- 20130918
LR  - 20131121
IS  - 1369-1600 (Electronic)
IS  - 1355-6215 (Linking)
VI  - 18
IP  - 2
DP  - 2013 Mar
TI  - Effects of repeated treatment with MDMA on working memory and behavioural 
      flexibility in mice.
PG  - 263-73
LID - 10.1111/j.1369-1600.2011.00421.x [doi]
AB  - Repeated administration of 3,4-methylenedioxymethamphetamine (MDMA) produces 
      dopaminergic neurotoxicity in mice. However, it is still not clear whether this 
      exposure induces deficits in cognitive processing related to specific subsets of 
      executive functioning. We evaluated the effects of neurotoxic and non-neurotoxic 
      doses of MDMA (0, 3 and 30 mg/kg, twice daily for 4 days) on working memory and 
      attentional set-shifting in mice, and changes in extracellular levels of dopamine 
      (DA) in the striatum. Treatment with MDMA (30 mg/kg) disrupted performance of 
      acquired operant alternation, and this impairment was still apparent 5 days after 
      the last drug administration. Decreased alternation was not related to anhedonia 
      because no differences were observed between groups in the saccharin preference 
      test under similar experimental conditions. Correct responding on delayed 
      alternation was increased 1 day after repeated treatment with MDMA (30 mg/kg), 
      probably because of general behavioural quiescence. Notably, the high dose 
      regimen of MDMA impaired attentional set-shifting related to an increase in total 
      perseveration errors. Finally, basal extracellular levels of DA in the striatum 
      were not modified in mice repeatedly treated with MDMA with respect to controls. 
      However, an acute challenge with MDMA (10 mg/kg) failed to increase DA outflow in 
      mice receiving the highest MDMA dose (30 mg/kg), corroborating a decrease in the 
      functionality of DA transporters. Seven days after this treatment, the effects of 
      MDMA on DA outflow were recovered. These results suggest that repeated neurotoxic 
      doses of MDMA produce lasting impairments in recall of alternation behaviour and 
      reduce cognitive flexibility in mice.
CI  - (c) 2012 The Authors, Addiction Biology (c) 2012 Society for the Study of Addiction.
FAU - Vinals, Xavier
AU  - Vinals X
AD  - Laboratory of Neuropharmacology, Pompeu Fabra University (UPF), Spain.
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 - 20120119
PL  - United States
TA  - Addict Biol
JT  - Addiction biology
JID - 9604935
RN  - 0 (Adrenergic Uptake Inhibitors)
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - FST467XS7D (Saccharin)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Adrenergic Uptake Inhibitors/administration & dosage/*pharmacology/toxicity
MH  - Analysis of Variance
MH  - Animals
MH  - Attention/drug effects
MH  - Conditioning, Operant/*drug effects
MH  - Corpus Striatum/*metabolism
MH  - Cues
MH  - Diet, High-Fat
MH  - Dopamine/*metabolism
MH  - Dopamine Plasma Membrane Transport Proteins/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Executive Function/drug effects
MH  - Food Preferences/drug effects
MH  - Haplorhini
MH  - Humans
MH  - Male
MH  - Memory, Short-Term/*drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microdialysis/methods
MH  - N-Methyl-3,4-methylenedioxyamphetamine/administration & 
      dosage/*pharmacology/toxicity
MH  - Rats
MH  - Saccharin/administration & dosage
EDAT- 2012/01/21 06:00
MHDA- 2013/09/21 06:00
CRDT- 2012/01/21 06:00
PHST- 2012/01/21 06:00 [entrez]
PHST- 2012/01/21 06:00 [pubmed]
PHST- 2013/09/21 06:00 [medline]
AID - 10.1111/j.1369-1600.2011.00421.x [doi]
PST - ppublish
SO  - Addict Biol. 2013 Mar;18(2):263-73. doi: 10.1111/j.1369-1600.2011.00421.x. Epub 
      2012 Jan 19.