Abstract
In vivo, ethanol alters the effect ofN-methyl-d-aspartate (NMDA) and GABA in some brain regions but is without effect in others. To determine whether these regional differences were due to differences in the effect of ethanol on postsynaptic NMDA or GABAA receptors, we examined the effect of ethanol on NMDA- and GABA-gated currents from neurons acutely dissociated from the lateral septal nucleus, substantia nigra, thalamus, hippocampus, and cerebellum. Ethanol decreased the effect of NMDA similarly in all brain areas tested and had similar effects on Chinese hamster ovary cells expressing NR2A or NR2B subunits with an NR1-1a subunit. However, ifenprodil reduced the inhibition by ethanol of NMDA-gated currents from neurons isolated from the lateral septum without affecting neurons from the substantia nigra. In contrast to the robust effect of ethanol on NMDA-gated currents, ethanol (25–300 mM) was without effect on GABA-gated currents at all brain sites tested or on Ltk− cells stably expressing the α1, β2, and γ2L or γ2S subunits. The neuroactive steroid alphaxalone profoundly enhanced GABA-gated currents in all brain areas and cell types tested, indicating a similar sensitivity to allosteric modulation; however, there was no interaction of alphaxalone with ethanol at any site tested. These data suggest that the regional differences in the effect of ethanol observed in vivo are not due to a differential action of ethanol at the postsynaptic NMDA or GABAA receptor subtypes.
Footnotes
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This study was supported by National Institutes of Health Grants AA-10025, AA-00253, and AA-12655.
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DOI: 10.1124/jpet.102.041590
- Abbreviations:
- NMDA
- N-methyl-d-aspartate
- SES
- standard external recording solution
- CHO
- Chinese hamster ovary
- HSD
- honestly significant difference
- HEK
- human embryonic kidney
- MK-801
- dizocilpine maleate
- Received July 18, 2002.
- Accepted September 23, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
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