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Effects of Ethanol on Excitatory and Inhibitory Synaptic Transmission in Rat Cortical Neurons

Authors

  • Shigeki Moriguchi,

    1. Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois
    2. Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
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  • Xilong Zhao,

    1. Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois
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  • William Marszalec,

    1. Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois
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  • Jay Z. Yeh,

    1. Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois
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  • Toshio Narahashi

    1. Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois
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Errata

This article is corrected by:

  1. Errata: Erratum Volume 31, Issue 3, xii, Article first published online: 12 February 2007

  • This work was supported by a grant from the National Institutes of Health R01 AA07836.

Reprint requests: Toshio Narahashi, Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, IL; E-mail: narahashi@northwestern.edu

Abstract

Background: The γ-aminobutyric acid-A (GABAA) receptor and glutamate receptors are among the most important target sites for the behavioral effects of ethanol. However, data in the literature concerning the ethanol modulation of the GABAA and glutamate receptors have been controversial. The activity of the neuronal nicotinic acetylcholine (ACh) receptors (nAChRs) has recently been reported to be potently augmented by ethanol. The activation of nAChRs is also known to cause the release of various neurotransmitters including GABA and glutamate. Thus, ethanol potentiation of nAChRs is expected to stimulate the GABAergic and glutamatergic systems.

Methods: Whole-cell patch clamp experiments were performed using rat cortical neurons in primary culture to record spontaneous miniature inhibitory postsynaptic currents (mIPSCs) and spontaneous miniature excitatory postsynaptic currents (mEPSCs).

Results: Two types of neurons were distinguished: bipolar neurons possessed α4β2 nAChRs generating a steady current in response to 30 nM ACh, and multipolar neurons that did not generate a current by ACh application. Acetylcholine greatly increased the frequency of mEPSCs and mIPSCs in bipolar neurons but not in multipolar neurons. The amplitude of neither type of neuron was affected by ACh. Ethanol at 10 to 100 mM suppressed the amplitude of mEPSCs while augmenting the amplitude of mIPSCs in both bipolar and multipolar neurons, indicating the direct action on the respective receptors. In bipolar neurons, ACh plus 100 mM ethanol greatly increased the frequency of mIPSCs beyond the levels achieved by ACh alone, while no such increases were observed in multipolar neurons.

Conclusions: It is concluded that ethanol stimulation of nAChRs modulates the activity of both glutamate and GABA receptors in rat cortical bipolar neurons.

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