PMID- 18419818
OWN - NLM
STAT- MEDLINE
DCOM- 20080529
LR  - 20211020
IS  - 1471-2202 (Electronic)
IS  - 1471-2202 (Linking)
VI  - 9
DP  - 2008 Apr 17
TI  - Extensive neuroadaptive changes in cortical gene-transcript expressions of the 
      glutamate system in response to repeated intermittent MDMA administration in 
      adolescent rats.
PG  - 39
LID - 10.1186/1471-2202-9-39 [doi]
AB  - BACKGROUND: Many studies have focused on the implication of the serotonin and 
      dopamine systems in neuroadaptive responses to the recreational drug 
      3,4-methylenedioxy-metamphetamine (MDMA). Less attention has been given to the 
      major excitatory neurotransmitter glutamate known to be implicated in 
      schizophrenia and drug addiction. The aim of the present study was to investigate 
      the effect of repeated intermittent MDMA administration upon gene-transcript 
      expression of the glutamate transporters (EAAT1, EAAT2-1, EAAT2-2), the glutamate 
      receptor subunits of AMPA (GluR1, GluR2, GluR3), the glutamate receptor subunits 
      of NMDA (NR1, NR2A and NR2B), as well as metabotropic glutamate receptors 
      (mGluR1, mGluR2, mGluR3, mGluR5) in six different brain regions. Adolescent male 
      Sprague Dawley rats received MDMA at the doses of 3 x 1 and 3 x 5 mg/kg/day, or 
      3x vehicle 3 hours apart, every 7th day for 4 weeks. The gene-transcript levels 
      were assessed using real-time PCR validated with a range of housekeeping genes. 
      RESULTS: The findings showed pronounced enhancements in gene-transcript 
      expression of GluR2, mGluR1, mGluR5, NR1, NR2A, NR2B, EAAT1, and EAAT2-2 in the 
      cortex at bregma +1.6. In the caudate putamen, mRNA levels of GluR3, NR2A, and 
      NR2B receptor subunits were significantly increased. In contrast, the 
      gene-transcript expression of GluR1 was reduced in the hippocampus. In the 
      hypothalamus, there was a significant increase of GluR1, GluR3, mGluR1, and 
      mGluR3 gene-transcript expressions. CONCLUSION: Repeated intermittent MDMA 
      administration induces neuroadaptive changes in gene-transcript expressions of 
      glutamatergic NMDA and AMPA receptor subunits, metabotropic receptors and 
      transporters in regions of the brain regulating reward-related associative 
      learning, cognition, and memory and neuro-endocrine functions.
FAU - Kindlundh-Hogberg, Anna M S
AU  - Kindlundh-Hogberg AM
AD  - Department of Neuroscience, Division of Functional Pharmacology, Uppsala 
      University, 751 24 Uppsala, Sweden. Anna.Kindlundh@neuro.uu.se
FAU - Blomqvist, Anna
AU  - Blomqvist A
FAU - Malki, Rana
AU  - Malki R
FAU - Schioth, Helgi B
AU  - Schioth HB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080417
PL  - England
TA  - BMC Neurosci
JT  - BMC neuroscience
JID - 100966986
RN  - 0 (Adrenergic Uptake Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, AMPA)
RN  - 0 (Receptors, Metabotropic Glutamate)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Vesicular Glutamate Transport Proteins)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Adaptation, Physiological/*drug effects/genetics
MH  - Adrenergic Uptake Inhibitors/pharmacology
MH  - Age Factors
MH  - Aging/metabolism
MH  - Amphetamine-Related Disorders/genetics/metabolism
MH  - Animals
MH  - Brain/anatomy & histology/*drug effects/*metabolism
MH  - Brain Chemistry/drug effects/genetics
MH  - Cerebral Cortex/anatomy & histology/drug effects/metabolism
MH  - Drug Administration Schedule
MH  - Gene Expression Regulation/*drug effects/genetics
MH  - Glutamic Acid/*metabolism
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Neuronal Plasticity/drug effects/genetics
MH  - RNA, Messenger/drug effects/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, AMPA/genetics
MH  - Receptors, Metabotropic Glutamate/genetics
MH  - Receptors, N-Methyl-D-Aspartate/genetics
MH  - Synaptic Transmission/drug effects/genetics
MH  - Vesicular Glutamate Transport Proteins/genetics
PMC - PMC2358913
EDAT- 2008/04/19 09:00
MHDA- 2008/05/30 09:00
PMCR- 2008/04/17
CRDT- 2008/04/19 09:00
PHST- 2007/12/18 00:00 [received]
PHST- 2008/04/17 00:00 [accepted]
PHST- 2008/04/19 09:00 [pubmed]
PHST- 2008/05/30 09:00 [medline]
PHST- 2008/04/19 09:00 [entrez]
PHST- 2008/04/17 00:00 [pmc-release]
AID - 1471-2202-9-39 [pii]
AID - 10.1186/1471-2202-9-39 [doi]
PST - epublish
SO  - BMC Neurosci. 2008 Apr 17;9:39. doi: 10.1186/1471-2202-9-39.