PMID- 20618412
OWN - NLM
STAT- MEDLINE
DCOM- 20100803
LR  - 20211020
IS  - 1528-1167 (Electronic)
IS  - 0013-9580 (Print)
IS  - 0013-9580 (Linking)
VI  - 51 Suppl 3
IP  - Suppl 3
DP  - 2010 Jul
TI  - Inverse relationship between seizure expression and extrasynaptic NMDAR function 
      following chronic NMDAR inhibition.
PG  - 102-5
LID - 10.1111/j.1528-1167.2010.02621.x [doi]
AB  - We showed previously that electrographic seizures involving dentate granule cells 
      in organotypic hippocampal slice cultures were dramatically reduced following 
      chronic treatment with the NR2B-selective antagonist, Ro25,6981, but were 
      increased following chronic treatment with the high-affinity competitive 
      antagonist, D(-)-2-amino-5-phosphonopentanoic acid (D-APV). To begin to 
      investigate the potential mechanisms underlying the differential effects of 
      N-methyl-D-aspartate receptor (NMDAR) antagonists on seizures, electrophysiologic 
      experiments were conducted in dentate granule cells in hippocampal slice cultures 
      treated for the entire 17-21 day culture period with vehicle, Ro25,6981 or D-APV. 
      Initial experiments revealed a lack of an association between miniature 
      excitatory postsynaptic current (mEPSC) measures and seizures suggesting that 
      shifts in mEPSC were unlikely to account for the differential effects of D-APV 
      and Ro25,6981 on seizures. However, the amplitude of tonic NMDAR-mediated 
      currents was reduced in cultures treated chronically with D-APV and dramatically 
      enhanced in cultures treated chronically with Ro25,6981. Because tonic NMDAR 
      currents are mediated primarily by extrasynaptic NMDAR, these data show an 
      inverse relationship between changes in extrasynaptic NMDAR function and 
      alterations in seizure expression.
FAU - Bausch, Suzanne B
AU  - Bausch SB
AD  - Department of Pharmacology, Uniformed Services University School of Medicine, 
      Bethesda, Maryland 20814-4799, USA. sbausch@usuhs.mil
FAU - He, Shuijin
AU  - He S
FAU - Dong, Yu
AU  - Dong Y
LA  - eng
GR  - R01 NS045964/NS/NINDS NIH HHS/United States
GR  - R01 NS045964-01A1/NS/NINDS NIH HHS/United States
GR  - NS045964/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Epilepsia
JT  - Epilepsia
JID - 2983306R
RN  - 0 (GABA-A Receptor Antagonists)
RN  - 0 (Phenols)
RN  - 0 (Piperidines)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Ro 25-6981)
SB  - IM
MH  - Animals
MH  - Dentate Gyrus/drug effects/physiopathology
MH  - Disease Models, Animal
MH  - GABA-A Receptor Antagonists
MH  - Hippocampus/drug effects/physiopathology
MH  - Phenols/pharmacology
MH  - Piperidines/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/drug effects/*physiology
MH  - Seizures/chemically induced/drug therapy/*etiology
MH  - Synaptic Transmission/drug effects
PMC - PMC2909021
MID - NIHMS195708
COIS- Disclosure: None of the authors has any conflict of interest to declare. We 
      confirm that we have read the Journal's position on issues involved in ethical 
      publication and affirm that this article is consistent with those guidelines.
EDAT- 2010/07/22 06:00
MHDA- 2010/08/04 06:00
PMCR- 2011/07/01
CRDT- 2010/07/13 06:00
PHST- 2010/07/13 06:00 [entrez]
PHST- 2010/07/22 06:00 [pubmed]
PHST- 2010/08/04 06:00 [medline]
PHST- 2011/07/01 00:00 [pmc-release]
AID - EPI2621 [pii]
AID - 10.1111/j.1528-1167.2010.02621.x [doi]
PST - ppublish
SO  - Epilepsia. 2010 Jul;51 Suppl 3(Suppl 3):102-5. doi: 
      10.1111/j.1528-1167.2010.02621.x.