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Pavlovian-to-instrumental transfer effects in the nucleus accumbens relate to relapse in alcohol dependence

  • In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n=31 detoxified patients diagnosed with alcohol dependence and n=24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, whichIn detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n=31 detoxified patients diagnosed with alcohol dependence and n=24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence.show moreshow less

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Author details:Maria GarbusowORCiDGND, Daniel SchadORCiDGND, Miriam Hannah SeboldORCiDGND, Eva Friedel, Nadine BernhardtORCiD, Stefan P. Koch, Bruno Steinacher, Norbert Kathmann, Dirk E. M. Geurts, Christian SommerORCiD, Dirk K. Mueller, Stephan NebeORCiD, Soeren Paul, Hans-Ulrich WittchenORCiDGND, Ulrich S. Zimmermann, Henrik Walter, Michael N. SmolkaORCiDGND, Philipp Sterzer, Michael Armin RappORCiDGND, Quentin J. M. HuysORCiD, Florian SchlagenhaufORCiDGND, Andreas HeinzORCiDGND
DOI:https://doi.org/10.1111/adb.12243
ISSN:1355-6215
ISSN:1369-1600
Pubmed ID:https://pubmed.ncbi.nlm.nih.gov/25828702
Title of parent work (English):Addiction biology
Publisher:Wiley-Blackwell
Place of publishing:Hoboken
Publication type:Article
Language:English
Year of first publication:2016
Publication year:2016
Release date:2020/03/22
Tag:human Pavlovian-to-instrumental transfer; nucleus accumbens; relapse in alcohol use disorder
Volume:21
Number of pages:13
First page:719
Last Page:731
Funding institution:German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) [FOR 1617, HE 2597/13-1, HE 2597/14-1, HE 2597/15-1, SCHL 1969/2-1, SM 80/7-1, STE 1430/6-1, RA 1047/2-1, WI 709/10-1, ZI 1119/3-1]; German Research Foundation (NeuroCure) [EXC 257]; Netherlands Organisation for Healthy Research and Development [AGIKO 92003576]
Peer review:Referiert
Institution name at the time of the publication:Humanwissenschaftliche Fakultät / Exzellenzbereich Kognitionswissenschaften
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