Does acetaldehyde mediate ethanol action in the central nervous system?

Maria Paola Mascia, Rajani Maiya, Cecilia M. Borghese, Ingrid A. Lobo, Koji Hara, Tomohiro Yamakura, Diane H. Gong, Michael J. Beckstead

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Background: Some of the effects of ethanol in the central nervous system are due to changes in function of ligand-gated ion channels. Production of detectable amounts of acetaldehyde, a primary metabolite of ethanol, has been demonstrated in brain homogenates. The aim of this study was to determine whether central actions that are often attributed to ethanol may actually be mediated by acetaldehyde. Methods: The effects of acetaldehyde (1-1000 μM) were tested by two-electrode voltage-clamp electrophysiology in Xenopus laevis oocytes expressing 10 different ligand-gated ion channel receptors [α1 glycine; α1β2γ2s γ-aminobutyric acid (GABA)A; ρ1 GABAc; 5-hydroxytryptamine-3A; NR1a/NR2A NMDA; GluR1/GluR2 AMPA; GluR6/KA2 kainate; and α4β2, α4β4, and α2β4 nicotinic-acetylcholine] and the G-protein-coupled inward rectifying potassium channel GIRK2. We also investigated the effect of acetaldehyde on the dopamine transporter (DAT), performing dopamine uptake assays in oocytes expressing DAT. Results: Acetaldehyde (1 and 10 μM) significantly enhanced αl glycine receptor-mediated currents. Acetaldehyde did not affect the function of any of the other receptors tested or the potassium currents measured in GIRK2 channels. Moreover, acetaldehyde did not alter the DAT-mediated dopamine uptake. Conclusions: Our results suggest a potential minor role for acetaldehyde in the glycine receptor-mediated effects of ethanol. Otherwise, acetaldehyde does not modulate function of the neuronal receptors tested in this study, in GIRK channels or DAT, when expressed recombinantly in Xenopus laevis oocytes.

Original languageEnglish (US)
Pages (from-to)1570-1575
Number of pages6
JournalAlcoholism: Clinical and Experimental Research
Volume25
Issue number11
DOIs
StatePublished - Jan 1 2001

Keywords

  • Acetaldehyde
  • Dopamine Transporter
  • Ethanol
  • GIRK
  • Ligand-Gated Ion Channels

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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