Effects of d-cycloserine on extinction of mesolimbic cue reactivity in alcoholism: a randomized placebo-controlled trial
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 behavi...
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| Published in | Psychopharmacology Vol. 232; no. 13; pp. 2353 - 2362 |
|---|---|
| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Berlin/Heidelberg
Springer Berlin Heidelberg
01.07.2015
Springer Springer Nature B.V |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0033-3158 1432-2072 1432-2072 |
| DOI | 10.1007/s00213-015-3882-5 |
Cover
| 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. |
|---|---|
| AbstractList | 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.RATIONALEMesocorticolimbic 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.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.OBJECTIVESIn 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.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.METHODSIn 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.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.RESULTSFollowing 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.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.CONCLUSIONSDCS 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. 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. Electronic supplementary material The online version of this article (doi:10.1007/s00213-015-3882-5) contains supplementary material, which is available to authorized users. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. |
| Audience | Academic |
| Author | Spanagel, Rainer Loeber, Sabine Kirsch, Martina Kiefer, Falk Mann, Karl Reinhard, Iris Jorde, Anne von der Goltz, Christoph Hoffmann, Sabine Vollstädt-Klein, Sabine Bach, Patrick |
| Author_xml | – sequence: 1 givenname: Falk surname: Kiefer fullname: Kiefer, Falk organization: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg – sequence: 2 givenname: Martina surname: Kirsch fullname: Kirsch, Martina organization: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg – sequence: 3 givenname: Patrick surname: Bach fullname: Bach, Patrick organization: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg – sequence: 4 givenname: Sabine surname: Hoffmann fullname: Hoffmann, Sabine organization: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg – sequence: 5 givenname: Iris surname: Reinhard fullname: Reinhard, Iris organization: Department of Biostatistics, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg – sequence: 6 givenname: Anne surname: Jorde fullname: Jorde, Anne organization: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg – sequence: 7 givenname: Christoph surname: von der Goltz fullname: von der Goltz, Christoph organization: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg – sequence: 8 givenname: Rainer surname: Spanagel fullname: Spanagel, Rainer organization: Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg – sequence: 9 givenname: Karl surname: Mann fullname: Mann, Karl organization: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg – sequence: 10 givenname: Sabine surname: Loeber fullname: Loeber, Sabine organization: Department of Clinical Psychology and Psychotherapy, University of Bamberg – sequence: 11 givenname: Sabine surname: Vollstädt-Klein fullname: Vollstädt-Klein, Sabine email: s.vollstaedt-klein@zi-mannheim.de organization: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25697860$$D View this record in MEDLINE/PubMed |
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Mesocorticolimbic reactivity to alcohol-associated cues has been shown to be associated with relapse to renewed drinking and to be decreased by... Mesocorticolimbic reactivity to alcohol-associated cues has been shown to be associated with relapse to renewed drinking and to be decreased by... Rationale Mesocorticolimbic reactivity to alcohol-associated cues has been shown to be associated with relapse to renewed drinking and to be decreased by... |
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| Title | Effects of d-cycloserine on extinction of mesolimbic cue reactivity in alcoholism: a randomized placebo-controlled trial |
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