Magnesium-Dependent Inhibition of N-Methyl-d-Aspartate Receptor-Mediated Synaptic Transmission by Ethanol1
- Divisions of 1Psychiatry (S.D.M.) and 2Neurology Research (W.A.W.), Durham VA Medical Center, and Departments of 3Psychiatry (J.L.C., S.D.M.) and 4Pharmacology (W.A.W.), Duke University Medical Center, Durham, North Carolina
Abstract
Previous studies have indicated that ethanol (EtOH) has a relatively specific effect on excitatory synaptic transmission by inhibiting function of the N-methyl-d-aspartate receptor. We have found that EtOH potently inhibits N-methyl-d-aspartate-mediated synaptic currents in the basolateral amygdala, a brain region associated with actions of anxiolytic agents such as EtOH. This inhibitory effect of EtOH requires the presence of magnesium (Mg++). The dependence of the effect of EtOH on the presence of Mg++ suggests a possible molecular site of the action of EtOH in the vicinity of Mg++ binding sites on the N-methyl-d-aspartate receptor-channel complex. Because EtOH consumption may result in reductions in free brain Mg++, this dynamic interaction between EtOH and Mg++ may have important implications for understanding the behavioral effects of EtOH.
Footnotes
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Send reprint requests to: Dr. Scott D. Moore, Room 25, Bldg 16, Durham VA Medical Center, Durham, NC 27705.
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↵1 This work was supported by VA Merit Review and NIAAA R 29 AA 10994-01.
- Abbreviations:
- EtOH
- ethanol
- Mg++
- magnesium
- NMDA
- N-methyl-d-aspartate
- ACSF
- artificial cerebrospinal fluid
- BMI
- bicuculline methiodide
- DNQX
- 6,7 dinitroquinoxaline
- HEPES
- 4-(2-hydroxyethyl)-piperazineethanesulfonic acid
- BAPTA
- 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’,-tetraacetic acid
- APV
- d,1-2-amino-5-phosphonovaleric acid
- GABA
- γ-aminobutyric acid
- EPSP
- excitatory postsynaptic potential
- EPSC
- excitatory postsynaptic current
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- Received March 12, 1998.
- Accepted June 1, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
