PMID- 17625498
OWN - NLM
STAT- MEDLINE
DCOM- 20080807
LR  - 20181113
IS  - 0893-133X (Print)
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Linking)
VI  - 33
IP  - 6
DP  - 2008 May
TI  - Alcohol inhibits NR2B-containing NMDA receptors in the ventral bed nucleus of the 
      stria terminalis.
PG  - 1379-90
AB  - Components of the mesolimbic dopamine system, in particular dopaminergic cells in 
      the ventral tegmental area (VTA), have been implicated in the acute reinforcing 
      actions of ethanol. The ventral bed nucleus of the stria terminalis (vBNST) 
      potently regulates dopaminergic cell firing in the VTA, and has been implicated 
      in the behavioral actions of ethanol. The N-methyl-D-asparate receptor (NMDAR) is 
      a major molecular target of ethanol, however, current evidence suggests that 
      ethanol regulation of NMDAR function is widely variable and likely depends on a 
      number of factors. Thus, it is critical to investigate ethanol regulation of 
      NMDAR function at synapses relevant to ethanol-regulated behaviors, such as in 
      the vBNST. Here we show, using multiple techniques, that ethanol inhibits NMDAR 
      function in vBNST neurons in a postsynaptic fashion. Further, we demonstrate the 
      functional presence of both NR2A and NR2B-containing NMDARs in the vBNST. While 
      genetic removal of NR2A did not alter the magnitude of ethanol inhibition, 
      pharmacological blockade of NR2B rendered synaptically activated NMDARs 
      insensitive to ethanol inhibition. Finally, we demonstrate that ethanol inhibits 
      NMDARs in cells in the vBNST that project to the VTA, providing a direct means by 
      which ethanol in the vBNST can modulate the dopaminergic system.
FAU - Kash, Thomas L
AU  - Kash TL
AD  - Department of Molecular Physiology and Biophysics, Vanderbilt University School 
      of Medicine, Nashville, TN 37232-0615, USA.
FAU - Matthews, Robert T
AU  - Matthews RT
FAU - Winder, Danny G
AU  - Winder DG
LA  - eng
GR  - U01 AA015635-01/AA/NIAAA NIH HHS/United States
GR  - F32 AA016025-03/AA/NIAAA NIH HHS/United States
GR  - U01 AA015635/AA/NIAAA NIH HHS/United States
GR  - R01 AA019455/AA/NIAAA NIH HHS/United States
GR  - F32 AA016025/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070711
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Central Nervous System Depressants)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (GABA Antagonists)
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 124-87-8 (Picrotoxin)
RN  - 3K9958V90M (Ethanol)
RN  - 6384-92-5 (N-Methylaspartate)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Central Nervous System Depressants/*administration & dosage
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Electric Stimulation
MH  - Ethanol/*administration & dosage
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Excitatory Postsynaptic Potentials/drug effects/physiology
MH  - GABA Antagonists/pharmacology
MH  - In Vitro Techniques
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Models, Biological
MH  - N-Methylaspartate/pharmacology
MH  - Patch-Clamp Techniques
MH  - Picrotoxin/pharmacology
MH  - Receptors, N-Methyl-D-Aspartate/deficiency/*metabolism
MH  - Septal Nuclei/cytology/*drug effects
PMC - PMC2864636
MID - NIHMS196721
COIS- DISCLOSURE/CONFLICT OF INTEREST Dr Kash declares that, except for income received 
      from primary employer, no financial support or compensation has been received 
      from any individual or corporate entity over the past 3 years for research or 
      professional service. Dr Matthews received compensation from Meharry Medical 
      College. Dr Winder received a distribution from Columbia University for the 
      licensing of transgenic mouse technology to Memory Pharmaceuticals and received a 
      consultancy fee from MEDAcorp. All of the authors declare that there are no 
      personal financial holdings that could be perceived as constituting a potential 
      conflict of interest.
EDAT- 2007/07/13 09:00
MHDA- 2008/08/08 09:00
PMCR- 2010/05/05
CRDT- 2007/07/13 09:00
PHST- 2007/07/13 09:00 [pubmed]
PHST- 2008/08/08 09:00 [medline]
PHST- 2007/07/13 09:00 [entrez]
PHST- 2010/05/05 00:00 [pmc-release]
AID - 1301504 [pii]
AID - 10.1038/sj.npp.1301504 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2008 May;33(6):1379-90. doi: 10.1038/sj.npp.1301504. 
      Epub 2007 Jul 11.