PMID- 25124230
OWN - NLM
STAT- MEDLINE
DCOM- 20150814
LR  - 20211021
IS  - 1559-1166 (Electronic)
IS  - 0895-8696 (Linking)
VI  - 54
IP  - 4
DP  - 2014 Dec
TI  - A study on the mechanism by which MDMA protects against dopaminergic dysfunction 
      after minimal traumatic brain injury (mTBI) in mice.
PG  - 684-97
LID - 10.1007/s12031-014-0399-z [doi]
AB  - Driving under methylenedioxymethamphetamine (MDMA) influence increases the risk 
      of being involved in a car accident, which in turn can lead to traumatic brain 
      injury. The behavioral deficits after traumatic brain injury (TBI) are closely 
      connected to dopamine pathway dysregulation. We have previously demonstrated in 
      mice that low MDMA doses prior to mTBI can lead to better performances in 
      cognitive tests. The purpose of this study was to assess in mice the changes in 
      the dopamine system that occurs after both MDMA and minimal traumatic brain 
      injury (mTBI). Experimental mTBI was induced using a concussive head trauma 
      device. One hour before injury, animals were subjected to MDMA. Administration of 
      MDMA before injury normalized the alterations in tyrosine hydroxylase (TH) levels 
      that were observed in mTBI mice. This normalization was also able to lower the 
      elevated dopamine receptor type 2 (D2) levels observed after mTBI. Brain-derived 
      neurotrophic factor (BDNF) levels did not change following injury alone, but in 
      mice subjected to MDMA and mTBI, significant elevations were observed. In the 
      behavioral tests, haloperidol reversed the neuroprotection seen when MDMA was 
      administered prior to injury. Altered catecholamine synthesis and high D2 
      receptor levels contribute to cognitive dysfunction, and strategies to normalize 
      TH signaling and D2 levels may provide relief for the deficits observed after 
      injury. Pretreatment with MDMA kept TH and D2 receptor at normal levels, allowing 
      regular dopamine system activity. While the beneficial effect we observe was due 
      to a dangerous recreational drug, understanding the alterations in dopamine and 
      the mechanism of dysfunction at a cellular level can lead to legal therapies and 
      potential candidates for clinical use.
FAU - Edut, S
AU  - Edut S
AD  - Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv 
      University, 69978, Tel Aviv, Israel, eshaha12@campus.haifa.ac.il.
FAU - Rubovitch, V
AU  - Rubovitch V
FAU - Rehavi, M
AU  - Rehavi M
FAU - Schreiber, S
AU  - Schreiber S
FAU - Pick, C G
AU  - Pick CG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140816
PL  - United States
TA  - J Mol Neurosci
JT  - Journal of molecular neuroscience : MN
JID - 9002991
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Catecholamines)
RN  - 0 (Receptors, Dopamine D2)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - J6292F8L3D (Haloperidol)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Brain/*drug effects/metabolism
MH  - Brain Concussion/*metabolism/prevention & control
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - Catecholamines/metabolism
MH  - Dopaminergic Neurons/drug effects/metabolism/physiology
MH  - Haloperidol/pharmacology
MH  - Mice
MH  - Mice, Inbred ICR
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology/therapeutic use
MH  - Receptors, Dopamine D2/genetics/*metabolism
MH  - Tyrosine 3-Monooxygenase/genetics/metabolism
EDAT- 2014/08/16 06:00
MHDA- 2015/08/15 06:00
CRDT- 2014/08/16 06:00
PHST- 2014/07/07 00:00 [received]
PHST- 2014/08/05 00:00 [accepted]
PHST- 2014/08/16 06:00 [entrez]
PHST- 2014/08/16 06:00 [pubmed]
PHST- 2015/08/15 06:00 [medline]
AID - 10.1007/s12031-014-0399-z [doi]
PST - ppublish
SO  - J Mol Neurosci. 2014 Dec;54(4):684-97. doi: 10.1007/s12031-014-0399-z. Epub 2014 
      Aug 16.