WWW.JNEUROSCI.ORG
-
The Journal of Neuroscience Introducing ALZET?ew Model 2006 Pump
QUICK SEARCH:   [advanced]


     
-


HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP
The Journal of Neuroscience, December 17, 2003, 23(37):11711-11724

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit an eLetter
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (42)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sanna, E.
Right arrow Articles by Biggio, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sanna, E.
Right arrow Articles by Biggio, G.

 Previous Article  |  Next Article 

Cellular/Molecular
Changes in GABAA Receptor Gene Expression Associated with Selective Alterations in Receptor Function and Pharmacology after Ethanol Withdrawal

Enrico Sanna,1,2 Maria Cristina Mostallino,1,2,4 Fabio Busonero,1,2 Giuseppe Talani,1,2 Stefania Tranquilli,1,2 Manuel Mameli,1,2 Saturnino Spiga,3 Paolo Follesa,1,2 and Giovanni Biggio1,2,4

1Department of Experimental Biology, Section of Neuroscience, 2Center of Excellence for the "Neurobiology of Dependence," and 3Department of Animal Biology and Ecology, University of Cagliari, 09123 Cagliari, Italy, and 4Consiglio Nazionale delle Ricerche, Institute of Neuroscience, 09123 Cagliari, Italy

Changes in the expression of subunits of the GABA type A (GABAA) receptor are implicated in the development of ethanol tolerance and dependence as well as in the central hyperexcitability associated with ethanol withdrawal. The impact of such changes on GABAA receptor function and pharmacological sensitivity was investigated with cultured rat hippocampal neurons exposed to ethanol for 5 d and then subjected to ethanol withdrawal. Both ethanol treatment and withdrawal were associated with a marked decrease in the maximal density of GABA-evoked Cl- currents, whereas the potency of GABA was unaffected. Ethanol exposure also reduced the modulatory efficacy of the benzodiazepine receptor agonists lorazepam, zolpidem, and zaleplon as well as that of the inverse agonists Ro 15-4513 and FG 7142, effects that were associated with a reduced abundance of mRNAs encoding the receptor subunits {alpha}1, {alpha}3, {gamma}2L, and {gamma}2S. Ethanol withdrawal restored the efficacy of lorazepam, but not that of low concentrations of zolpidem or zaleplon, to control values. Flumazenil, which was ineffective in control neurons, and Ro 15-4513 each potentiated the GABA response after ethanol withdrawal. These effects of withdrawal were accompanied by upregulation of the {alpha}2, {alpha}3, and {alpha}4 subunit mRNAs as well as of the {alpha}4 protein. Diazepam or {gamma}-hydroxybutyrate, but not baclofen, prevented the changes in both GABAA receptor pharmacology and subunit mRNA levels induced by ethanol withdrawal. Changes in GABAA receptor gene expression induced by prolonged exposure to and withdrawal of ethanol are thus associated with altered GABAA receptor function and pharmacological sensitivity.

Key words: GABAA receptor; ethanol; tolerance; dependence; gene expression; hippocampal neurons; patch clamp; {gamma}-hydroxybutyrate; diazepam

Received July 1, 2003; revised October 16, 2003; accepted October 17, 2003.




This article has been cited by other articles:


Home page
 J. Neurol. Neurosurg. PsychiatryHome page
A McKeon, M A Frye, and N. Delanty
The alcohol withdrawal syndrome
J. Neurol. Neurosurg. Psychiatry, August 1, 2008; 79(8): 854 - 862.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
L. Pignataro, A. N. Miller, L. Ma, S. Midha, P. Protiva, D. G. Herrera, and N. L. Harrison
Alcohol Regulates Gene Expression in Neurons via Activation of Heat Shock Factor 1
J. Neurosci., November 21, 2007; 27(47): 12957 - 12966.
[Abstract] [Full Text] [PDF]

Home page
 Arch Gen PsychiatryHome page
J. H. Krystal, J. Staley, G. Mason, I. L. Petrakis, J. Kaufman, R. A. Harris, J. Gelernter, and J. Lappalainen
{gamma}-Aminobutyric Acid Type A Receptors and Alcoholism: Intoxication, Dependence, Vulnerability, and Treatment.
Arch Gen Psychiatry, September 1, 2006; 63(9): 957 - 968.
[Abstract] [Full Text] [PDF]

Home page
 Arch Gen PsychiatryHome page
J. K. Staley, C. Gottschalk, I. L. Petrakis, R. Gueorguieva, S. O'Malley, R. Baldwin, P. Jatlow, N. P. L. G. Verhoeff, E. Perry, D. Weinzimmer, et al.
Cortical {gamma}-Aminobutyric Acid Type A-Benzodiazepine Receptors in Recovery From Alcohol Dependence: Relationship to Features of Alcohol Dependence and Cigarette Smoking
Arch Gen Psychiatry, August 1, 2005; 62(8): 877 - 888.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Ma, L. Song, G. E. Radoi, and N. L. Harrison
Transcriptional Regulation of the Mouse Gene Encoding the {alpha}-4 Subunit of the GABAA Receptor
J. Biol. Chem., September 24, 2004; 279(39): 40451 - 40461.
[Abstract] [Full Text] [PDF]


-

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help
-
Copyright 2008 by Society for Neuroscience ONLINE ISSN: 1529-2401
-