title: Effects of D-cycloserine on extinction of mesolimbic cue reactivity in alcoholism: a randomized placebo-controlled trial.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Square J5, 68159, Heidelberg, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Kiefer
authors.affiliation: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Square J5, 68159, Heidelberg, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Kirsch
authors.affiliation: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Square J5, 68159, Heidelberg, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Bach
authors.affiliation: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Square J5, 68159, Heidelberg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hoffmann
authors.affiliation: Department of Biostatistics, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Reinhard
authors.affiliation: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Square J5, 68159, Heidelberg, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Jorde
authors.affiliation: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Square J5, 68159, Heidelberg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: von der Goltz
authors.affiliation: Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Spanagel
authors.affiliation: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Square J5, 68159, Heidelberg, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Mann
authors.affiliation: Department of Clinical Psychology and Psychotherapy, University of Bamberg, Bamberg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Loeber
authors.affiliation: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Square J5, 68159, Heidelberg, Germany. s.vollstaedt-klein@zi-mannheim.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Vollstädt-Klein
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000188:drug therapy / Q000378:metabolism / Q000523:psychology; D000437:Alcoholism / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003463:Cues; D003523:Cycloserine / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D005108:Extinction, Psychological / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D008032:Limbic System / Q000187:drug effects* / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D013695:Temperance; D016896:Treatment Outcome
chemical_list: D003523:Cycloserine
keywords: Addiction; Alcoholism; Cue reactivity; Cue-exposure-based extinction; D-Cycloserine; fMRI