GABA Systems, Benzodiazepines, and Substance Dependence
Robert J. Malcolm, MD
Forgot your login? GET HELP
Alterations in the γ-aminobutyric acid (GABA) receptor complex and GABA neurotransmission
influence the reinforcing and intoxicating effects of alcohol and benzodiazepines. Chronic modulation
of the GABAA-benzodiazepine receptor complex plays a major role in central nervous system
dysregulation during alcohol abstinence. Withdrawal symptoms stem in part from a decreased
GABAergic inhibitory function and an increase in glutamatergic excitatory function. GABAA receptors play a role in both reward and withdrawal phenomena from alcohol and sedative-hypnotics.
Although less well understood, GABAB receptor complexes appear to play a role in inhibition of motivation and diminish relapse potential to reinforcing drugs. Evidence suggests that long-term alcohol
use and concomitant serial withdrawals permanently alter GABAergic function, down-regulate benzodiazepine
binding sites, and in preclinical models lead to cell death. Benzodiazepines have substantial
drawbacks in the treatment of substance use–related disorders that include interactions with alcohol,
rebound effects, alcohol priming, and the risk of supplanting alcohol dependency with addiction
to both alcohol and benzodiazepines. Polysubstance-dependent individuals frequently self-medicate
with benzodiazepines. Selective GABA agents with novel mechanisms of action have anxiolytic,
anticonvulsant, and reward inhibition profiles that have potential in treating substance use and withdrawal and enhancing relapse prevention with less liability than benzodiazepines. The GABAB
receptor agonist baclofen has promise in relapse prevention in a number of substance dependence disorders.
The GABAA and GABAB pump reuptake inhibitor tiagabine has potential for managing
alcohol and sedative-hypnotic withdrawal and also possibly a role in relapse prevention.
J Clin Psychiatry 2003;64(suppl 3):36-40
© Copyright 2003 Physicians Postgraduate Press, Inc.
Manage Subscriptions
/_layouts/images/ReportServer/Manage_Subscription.gif
/JCP/article/_layouts/ReportServer/ManageSubscriptions.aspx?list={ListId}&ID={ItemId}
0x80
0x0
FileType
rdl
350
Manage Data Sources
/JCP/article/_layouts/ReportServer/DataSourceList.aspx?list={ListId}&ID={ItemId}
0x0
0x20
FileType
rdl
351
Manage Shared Datasets
/JCP/article/_layouts/ReportServer/DatasetList.aspx?list={ListId}&ID={ItemId}
0x0
0x20
FileType
rdl
352
Manage Parameters
/JCP/article/_layouts/ReportServer/ParameterList.aspx?list={ListId}&ID={ItemId}
0x0
0x4
FileType
rdl
353
Manage Processing Options
/JCP/article/_layouts/ReportServer/ReportExecution.aspx?list={ListId}&ID={ItemId}
0x0
0x4
FileType
rdl
354
Manage Cache Refresh Plans
/JCP/article/_layouts/ReportServer/CacheRefreshPlanList.aspx?list={ListId}&ID={ItemId}
0x0
0x4
FileType
rdl
355
View Report History
/JCP/article/_layouts/ReportServer/ReportHistory.aspx?list={ListId}&ID={ItemId}
0x0
0x40
FileType
rdl
356
View Dependent Items
/JCP/article/_layouts/ReportServer/DependentItems.aspx?list={ListId}&ID={ItemId}
0x0
0x4
FileType
rsds
350
Edit Data Source Definition
/JCP/article/_layouts/ReportServer/SharedDataSource.aspx?list={ListId}&ID={ItemId}
0x0
0x4
FileType
rsds
351
View Dependent Items
/JCP/article/_layouts/ReportServer/DependentItems.aspx?list={ListId}&ID={ItemId}
0x0
0x4
FileType
smdl
350
Manage Clickthrough Reports
/JCP/article/_layouts/ReportServer/ModelClickThrough.aspx?list={ListId}&ID={ItemId}
0x0
0x4
FileType
smdl
352
Manage Model Item Security
/JCP/article/_layouts/ReportServer/ModelItemSecurity.aspx?list={ListId}&ID={ItemId}
0x0
0x2000000
FileType
smdl
353
Regenerate Model
/JCP/article/_layouts/ReportServer/GenerateModel.aspx?list={ListId}&ID={ItemId}
0x0
0x4
FileType
smdl
354
Manage Data Sources
/JCP/article/_layouts/ReportServer/DataSourceList.aspx?list={ListId}&ID={ItemId}
0x0
0x20
FileType
smdl
351
Load in Report Builder
/JCP/article/_layouts/ReportServer/RSAction.aspx?RSAction=ReportBuilderModelContext&list={ListId}&ID={ItemId}
0x0
0x2
FileType
smdl
250
Edit in Report Builder
/_layouts/images/ReportServer/EditReport.gif
/JCP/article/_layouts/ReportServer/RSAction.aspx?RSAction=ReportBuilderReportContext&list={ListId}&ID={ItemId}
0x0
0x4
FileType
rdl
250
Edit in Report Builder
/JCP/article/_layouts/ReportServer/RSAction.aspx?RSAction=ReportBuilderDatasetContext&list={ListId}&ID={ItemId}
0x0
0x4
FileType
rsd
250
Manage Caching Options
/JCP/article/_layouts/ReportServer/DatasetCachingOptions.aspx?list={ListId}&ID={ItemId}
0x0
0x4
FileType
rsd
350
Manage Cache Refresh Plans
/JCP/article/_layouts/ReportServer/CacheRefreshPlanList.aspx?list={ListId}&ID={ItemId}&IsDataset=true
0x0
0x4
FileType
rsd
351
Manage Data Sources
/JCP/article/_layouts/ReportServer/DataSourceList.aspx?list={ListId}&ID={ItemId}
0x0
0x20
FileType
rsd
352
View Dependent Items
/JCP/article/_layouts/ReportServer/DependentItems.aspx?list={ListId}&ID={ItemId}
0x0
0x4
FileType
rsd
353
Compliance Details
javascript:commonShowModalDialog('{SiteUrl}/_layouts/itemexpiration.aspx?ID={ItemId}&List={ListId}', 'center:1;dialogHeight:500px;dialogWidth:500px;resizable:yes;status:no;location:no;menubar:no;help:no', function GotoPageAfterClose(pageid){if(pageid == 'hold') {STSNavigate(unescape(decodeURI('{SiteUrl}'))+'/_layouts/hold.aspx?ID={ItemId}&List={ListId}'); return false;} if(pageid == 'audit') {STSNavigate(unescape(decodeURI('{SiteUrl}'))+'/_layouts/Reporting.aspx?Category=Auditing&backtype=item&ID={ItemId}&List={ListId}'); return false;} if(pageid == 'config') {STSNavigate(unescape(decodeURI('{SiteUrl}'))+'/_layouts/expirationconfig.aspx?ID={ItemId}&List={ListId}'); return false;}}, null); return false;
0x0
0x1
ContentType
0x01
898
Document Set Version History
javascript:SP.UI.ModalDialog.ShowPopupDialog('{SiteUrl}/_layouts/DocSetVersions.aspx?List={ListId}&ID={ItemId}')
0x0
0x0
ContentType
0x0120D520
330
Send To other location
javascript:GoToPage('{SiteUrl}/_layouts/docsetsend.aspx?List={ListId}&ID={ItemId}')
0x0
0x0
ContentType
0x0120D520
350