PMID- 2575162
OWN - NLM
STAT- MEDLINE
DCOM- 19900212
LR  - 20190510
IS  - 0022-3751 (Print)
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Linking)
VI  - 414
DP  - 1989 Jul
TI  - Effects of new non-N-methyl-D-aspartate antagonists on synaptic transmission in 
      the in vitro rat hippocampus.
PG  - 317-36
AB  - 1. The effects of new, potent non-N-methyl-D-aspartate (NMDA) receptor 
      antagonists, 6,7-dinitroquinoxaline-2,3-dione (DNQX) and 
      6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), have been examined using intra- and 
      extracellular recordings in the hippocampal slice preparation. In terms of 
      potency and selectivity, the action of the two blockers was similar and CNQX was 
      used in most experiments. 2. CNQX reduced the responses to ionophoretic 
      applications of the non-NMDA agonists kainate (KAI) and quisqualate (QUIS) with 
      IC50 values of 1.2 and 4.8 microM, respectively. In Mg2+-free solutions responses 
      to NMDA were generally not affected by concentrations of CNQX up to 25 microM. 3. 
      The action of CNQX was only slowly and poorly reversible on washing. Responses to 
      QUIS and KAI were also reversibly reduced by ionophoretic application of CNQX. 4. 
      CNQX blocked the evoked EPSP in CA1 and CA3 neurones with an IC50 of around 2 
      microM, which is similar to the IC50 for responses to KAI. CNQX was without 
      effect on the passive membrane properties, the afferent volley and paired pulse 
      potentiation. 5. In the presence of CNQX (greater than 5 microM) a small EPSP 
      remained which was largest in CA1 neurones. It was blocked by low concentrations 
      of the NMDA receptor antagonist (+/-)-2-amino-5-phosphonovaleric acid (APV), was 
      markedly enhanced on removing Mg2+ ions from the bathing medium and, in 
      voltage-clamp experiments, showed a potential dependence which is characteristic 
      of the NMDA ionophore. 6. The latency of the APV-sensitive EPSP in CA1 was the 
      same as the CNQX-sensitive EPSP, indicating that NMDA receptors participate in 
      monosynaptic excitation. 7. Feedback and feed-forward inhibition in both area CA1 
      and CA3 were sensitive to CNQX. There seemed to be two components of the 
      inhibition, both of which appear to be GABAergic since they could be blocked by 
      picrotoxin (PTX), but only one of which was blocked by CNQX. The CNQX-resistant 
      IPSP was not affected by APV. 8. In conclusion, quinoxalinediones have been used 
      to demonstrate that non-NMDA receptors mediate the majority of the EPSP. 
      Additionally, a component of the EPSP in CA1 is mediated by NMDA receptors and is 
      manifested at resting membrane potentials and in the presence of Mg2+.
FAU - Andreasen, M
AU  - Andreasen M
AD  - Institute of Physiology, University of Aarhus, Denmark.
FAU - Lambert, J D
AU  - Lambert JD
FAU - Jensen, M S
AU  - Jensen MS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - 0 (Neuromuscular Depolarizing Agents)
RN  - 0 (Oxadiazoles)
RN  - 0 (Quinoxalines)
RN  - 62T278S1MX (FG 9041)
RN  - 6OTE87SCCW (6-Cyano-7-nitroquinoxaline-2,3-dione)
RN  - 8OC22C1B99 (Quisqualic Acid)
RN  - SIV03811UC (Kainic Acid)
SB  - IM
MH  - 6-Cyano-7-nitroquinoxaline-2,3-dione
MH  - Animals
MH  - Evoked Potentials
MH  - Hippocampus/*physiology
MH  - In Vitro Techniques
MH  - Kainic Acid/pharmacology
MH  - Neuromuscular Depolarizing Agents
MH  - Oxadiazoles/pharmacology
MH  - Quinoxalines/*pharmacology
MH  - Quisqualic Acid
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Synapses/drug effects/*physiology
MH  - *Synaptic Transmission/drug effects
PMC - PMC1189144
EDAT- 1989/07/01 00:00
MHDA- 1989/07/01 00:01
PMCR- 1989/07/01
CRDT- 1989/07/01 00:00
PHST- 1989/07/01 00:00 [pubmed]
PHST- 1989/07/01 00:01 [medline]
PHST- 1989/07/01 00:00 [entrez]
PHST- 1989/07/01 00:00 [pmc-release]
AID - 10.1113/jphysiol.1989.sp017690 [doi]
PST - ppublish
SO  - J Physiol. 1989 Jul;414:317-36. doi: 10.1113/jphysiol.1989.sp017690.