Does acetaldehyde mediate ethanol action in the central nervous system?

Citation
Mp. Mascia et al., Does acetaldehyde mediate ethanol action in the central nervous system?, ALC CLIN EX, 25(11), 2001, pp. 1570-1575
Citations number
27
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Clinical Psycology & Psychiatry","Neurosciences & Behavoir
Journal title
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
ISSN journal
0145-6008 → ACNP
Volume
25
Issue
11
Year of publication
2001
Pages
1570 - 1575
Database
ISI
SICI code
0145-6008(200111)25:11<1570:DAMEAI>2.0.ZU;2-D
Abstract
Background: Some of the effects of ethanol in the central nervous system ar e due to changes in function of ligand-gated ion channels. Production of de tectable 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 b e mediated by acetaldehyde. Methods: The effects of acetaldehyde (1-1000 muM) were tested by two-electr ode voltage-clamp electrophysiology in Xenopus laevis oocytes expressing 10 different ligand-gated ion channel receptors [alpha (1) glycine; alpha (1) beta (2)gamma (2S) gamma -aminobutyric acid (GABA)(A); rho (1) GABA(c); 5-h ydroxytryptamine-3A; NR1a/NR2A NMDA; GluR1/GluR2 AMPA, GluR6/KA2 kainate; a nd alpha (4)beta (2), alpha (4)beta (4), and alpha (2)beta (4) nicotinic-ac etylcholine] and the G-protein-coupled inward rectifying potassium channel GIRK2. We also investigated the effect of acetaldehyde on the dopamine tran sporter (DAT), performing dopamine uptake assays in oocytes expressing DAT. Results: Acetaldehyde (1 and 10 muM) significantly enhanced ce, glycine rec eptor-mediated currents. Acetaldehyde did not affect the function of any of the other receptors tested or the potassium currents measured in GIRK2 cha nnels. Moreover, acetaldehyde did not alter the DAT-mediated dopamine uptak e. 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 ooc ytes.