Effects of d-cycloserine on extinction of mesolimbic cue reactivity in alcoholism: a randomized placebo-controlled trial
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- 作者：Falk Kiefer ; Martina Kirsch ; Patrick Bach ; Sabine Hoffmann…
- 关键词：fMRI ; Addiction ; Alcoholism ; Cue reactivity ; Cue ; exposure ; based extinction ; d ; Cycloserine
- 刊名：Psychopharmacology
- 出版年：2015
- 出版时间：July 2015
- 年：2015
- 卷：232
- 期：13
- 页码：2353-2362
- 全文大小：667 KB
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Martina Kirsch (1)
Patrick Bach (1)
Sabine Hoffmann (1)
Iris Reinhard (2)
Anne Jorde (1)
Christoph von der Goltz (1)
Rainer Spanagel (3)
Karl Mann (1)
Sabine Loeber (4)
Sabine Vollst?dt-Klein (1)
1. Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Square J5, 68159, Heidelberg, Germany
2. Department of Biostatistics, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany
3. Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany
4. Department of Clinical Psychology and Psychotherapy, University of Bamberg, Bamberg, Germany - 刊物类别：Biomedical and Life Sciences
- 刊物主题：Biomedicine
Pharmacology and Toxicology
Psychiatry - 出版者：Springer Berlin / Heidelberg
- ISSN：1432-2072
文摘
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.