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Computational modelling reveals contrasting effects on reinforcement learning and cognitive flexibility in stimulant use disorder and obsessive-compulsive disorder: remediating effects of dopaminergic D2/3 receptor agents

Psychopharmacology, 2019-08, Vol.236 (8), p.2337-2358 [Peer Reviewed Journal]

The Author(s) 2019 ;COPYRIGHT 2019 Springer ;Psychopharmacology is a copyright of Springer, (2019). All Rights Reserved. © 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;ISSN: 0033-3158 ;EISSN: 1432-2072 ;DOI: 10.1007/s00213-019-05325-w ;PMID: 31324936

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Title:
Computational modelling reveals contrasting effects on reinforcement learning and cognitive flexibility in stimulant use disorder and obsessive-compulsive disorder: remediating effects of dopaminergic D2/3 receptor agents
Author: Kanen, Jonathan W. ; Ersche, Karen D. ; Fineberg, Naomi A. ; Robbins, Trevor W. ; Cardinal, Rudolf N.
Subjects: Adult ; Analysis ; Bayesian analysis ; Biomedical and Life Sciences ; Biomedicine ; Central Nervous System Stimulants - therapeutic use ; Cognition - drug effects ; Cognition - physiology ; Cognitive ability ; Computer applications ; Computer simulation ; Computer-generated environments ; Dopamine Agonists - pharmacology ; Dopamine Agonists - therapeutic use ; Dopamine Antagonists - pharmacology ; Dopamine Antagonists - therapeutic use ; Dopamine D2 Receptor Antagonists - pharmacology ; Dopamine D2 receptors ; Double-Blind Method ; Drug addiction ; Female ; Flexibility ; Humans ; Male ; Mathematical models ; Middle Aged ; Models, Neurological ; Neurosciences ; Neuroses ; Obsessive compulsive disorder ; Obsessive-Compulsive Disorder - drug therapy ; Obsessive-Compulsive Disorder - metabolism ; Obsessive-Compulsive Disorder - psychology ; Original Investigation ; Pharmacology/Toxicology ; Pramipexole ; Psychiatry ; Punishment ; Receptors, Dopamine D2 - agonists ; Receptors, Dopamine D2 - metabolism ; Receptors, Dopamine D3 - agonists ; Receptors, Dopamine D3 - antagonists & inhibitors ; Receptors, Dopamine D3 - metabolism ; Reinforcement ; Reinforcement, Psychology ; Reversal learning ; Reversal Learning - drug effects ; Reversal Learning - physiology ; Reward ; Substance-Related Disorders - drug therapy ; Substance-Related Disorders - metabolism ; Substance-Related Disorders - psychology ; Young Adult
Is Part Of: Psychopharmacology, 2019-08, Vol.236 (8), p.2337-2358
Description: Rationale Disorders of compulsivity such as stimulant use disorder (SUD) and obsessive-compulsive disorder (OCD) are characterised by deficits in behavioural flexibility, some of which have been captured using probabilistic reversal learning (PRL) paradigms. Objectives This study used computational modelling to characterise the reinforcement learning processes underlying patterns of PRL behaviour observed in SUD and OCD and to show how the dopamine D 2/3 receptor agonist pramipexole and the D 2/3 antagonist amisulpride affected these responses. Methods We applied a hierarchical Bayesian method to PRL data across three groups: individuals with SUD, OCD, and healthy controls. Participants completed three sessions where they received placebo, pramipexole, and amisulpride, in a double-blind placebo-controlled, randomised design. We compared seven models using a bridge sampling estimate of the marginal likelihood. Results Stimulus-bound perseveration, a measure of the degree to which participants responded to the same stimulus as before irrespective of outcome, was significantly increased in SUD, but decreased in OCD, compared to controls (on placebo). Individuals with SUD also exhibited reduced reward-driven learning, whilst both the SUD and OCD groups showed increased learning from punishment (nonreward). Pramipexole and amisulpride had similar effects on the control and OCD groups; both increased punishment-driven learning. These D 2/3 -modulating drugs affected the SUD group differently, remediating reward-driven learning and reducing aspects of perseverative behaviour, amongst other effects. Conclusions We provide a parsimonious computational account of how perseverative tendencies and reward- and punishment-driven learning differentially contribute to PRL in SUD and OCD. D 2/3 agents modulated these processes and remediated deficits in SUD in particular, which may inform therapeutic effects.
Publisher: Berlin/Heidelberg: Springer Berlin Heidelberg
Language: English
Identifier: ISSN: 0033-3158
EISSN: 1432-2072
DOI: 10.1007/s00213-019-05325-w
PMID: 31324936
Source: ProQuest One Psychology
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ProQuest Central

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Computational modelling reveals contrasting effects on reinforcement learning and cognitive flexibility in stimulant use disorder and obsessive-compulsive disorder: remediating effects of dopaminergic D2/3 receptor agents

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