Abstract:
RATIONALE:Mesocorticolimbic reactivity to alcohol-associated cues has been shown to be associated with relapse to renewed drinking and to be decreased by cue-exposure-based extinction training (CET). Evidence from preclinical studies suggests that the extinction of conditioned alcohol-seeking behavior might be facilitated by drugs increasing N-methyl-D-aspartate (NMDA) receptor-associated memory consolidation. OBJECTIVES:In this study, we assessed the efficacy of CET treatment supplemented with the partial NMDA-receptor agonist D-cycloserine (DCS) at reducing mesolimbic cue reactivity (CR), craving, and relapse risk in alcoholism. METHODS:In a randomized, placebo-controlled, double-blind study, we recruited 76 recently detoxified abstinent alcohol-dependent patients. Thirty-two (16 DCS, 16 placebo) patients showed cue-induced ventral-striatal activation measured with functional magnetic resonance imaging (fMRI) prior to treatment and were thus included in the efficacy analyses. After inpatient detoxification, patients underwent nine sessions of CET spaced over 3 weeks, receiving either 50 mg DCS or placebo 1 h prior to each CET session. FMRI was conducted before treatment and 3 weeks after treatment onset. RESULTS:Following treatment with CET plus DCS, cue-induced brain activation in the ventral and dorsal striatum was decreased compared to treatment with CET plus placebo. Elevated posttreatment ventral striatal CR and increased craving (assessed using the Obsessive Compulsive Drinking Scale) were associated with increased relapse risk. CONCLUSIONS:DCS was shown to augment the effect of CET for alcohol-dependent subjects. The interaction between craving and ventral-striatal CR on treatment outcome suggests that CET might be especially effective in patients exhibiting both high craving and elevated CR.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Kiefer F,Kirsch M,Bach P,Hoffmann S,Reinhard I,Jorde A,von der Goltz C,Spanagel R,Mann K,Loeber S,Vollstädt-Klein Sdoi
10.1007/s00213-015-3882-5subject
Has Abstractpub_date
2015-07-01 00:00:00pages
2353-62issue
13eissn
0033-3158issn
1432-2072pii
10.1007/s00213-015-3882-5journal_volume
232pub_type
杂志文章,随机对照试验abstract::Intracerebroventricular injections of gamma-aminobutyric acid (GABA) and of the GABA-transaminase inhibitor, ethanolamine-O-sulphate (EOS), decreased the food intake of freely-fed (GABA and EOS) and food-deprived rats (EOS). The effect, still evident 24 h after treatment, was not decreased by the GABA receptor-blocker...
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pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Psychopharmacology
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journal_title:Psychopharmacology
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更新日期:2012-08-01 00:00:00
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pub_type: 临床试验,杂志文章
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journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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pub_type: 杂志文章,评审
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更新日期:2012-01-01 00:00:00
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journal_title:Psychopharmacology
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更新日期:2003-02-01 00:00:00